Heart valve prosthesis

ABSTRACT

Heart valve prosthesis are disclosed that include a frame or support structure having an inflow portion, a valve-retaining tubular or central portion and a pair of support arms. The inflow portion radially extends from a first end of the valve-retaining tubular portion and the pair of support arms are circumferentially spaced apart and radially extend from an opposing second end of the valve-retaining tubular portion.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.13/572,842 filed Aug. 13, 2012, and is a continuation-in-part of U.S.application Ser. No. 13/736,460 filed Jan. 8, 2013, each of which isincorporated by reference herein in its entirety. This application alsoclaims the benefit of U.S. Provisional Appl. No. 61/822,616 filed May13, 2013, and U.S. Provisional Appl. No. 61/895,106 filed Oct. 24, 2013,each of which is incorporated by reference herein in its entirety.

FIELD OF THE INVENTION

The present invention is directed to heart valve prosthesis and methodsof percutaneously delivering heart valve prosthesis to a targetlocation.

BACKGROUND OF THE INVENTION

A human heart includes four heart valves that determine the pathway ofblood flow through the heart: the mitral valve, the tricuspid valve, theaortic valve, and the pulmonary valve. The mitral and tricuspid valvesare atrioventricular valves, which are between the atria and theventricles, while the aortic and pulmonary valves are semilunar valves,which are in the arteries leaving the heart. Ideally, native leaflets ofa heart valve move apart from each other when the valve is in an openposition, and meet or “coapt” when the valve is in a closed position.Problems that may develop with valves include stenosis in which a valvedoes not open properly, and/or insufficiency or regurgitation in which avalve does not close properly. Stenosis and insufficiency may occurconcomitantly in the same valve. The effects of valvular dysfunctionvary, with regurgitation or backflow typically having relatively severephysiological consequences to the patient.

Recently, prosthetic valves supported by stent structures that can bedelivered percutaneously using a catheter-based delivery system havebeen developed for heart and venous valve replacement. These prostheticvalves may include either self-expanding or balloon-expandable stentstructures with valve leaflets attached to the interior of the stentstructure. The prosthetic valve can be reduced in diameter, by crimpingonto a balloon catheter or by being contained within a sheath componentof a delivery catheter, and advanced through the venous or arterialvasculature. Once the prosthetic valve is positioned at the treatmentsite, for instance within an incompetent native valve, the stentstructure may be expanded to hold the prosthetic valve firmly in place.One example of a stented prosthetic valve is disclosed in U.S. Pat. No.5,957,949 to Leonhardt et al., which is incorporated by reference hereinin its entirety.

Due to the different physical characteristics of the mitral valve andits location within the heart, percutaneous implantation of a prostheticheart valve in the mitral position has its own unique requirements forprosthetic valve structure and replacement methods. Accordingly, thereis a continued need to provide improved mitral valve replacement devicesand methods for replacing the mitral valve percutaneously.

BRIEF SUMMARY OF THE INVENTION

Certain embodiments in accordance herewith are directed to valveprosthesis for implantation into a native valve site of an individual,such as a native cardiac or heart valve site, that may include a valvebody or component and a frame supporting the valve body. The frame mayinclude an inlet portion configured to engage the floor of the outflowtract of the native heart atrium and restrict movement of the valveprosthesis in a downstream direction of blood flow at the valve site. Insome embodiments in accordance herewith, the inlet portion can besubstantially s-shaped.

Certain embodiments in accordance herewith are directed to valveprosthesis that include a valve body or component and a frame supportingthe valve body, wherein the frame may include a central portionconfigured to fit securely within an annulus of the native valve site.The central portion may have an hourglass shape configured to pinch theannulus in order to provide axial fixation of the valve prosthesiswithin the valve site.

Certain embodiments in accordance herewith are directed to valveprosthesis that may include a valve body or component and a framesupporting the valve body, wherein the frame may include a centralportion configured to fit securely within an annulus of the valve site,a support arm extending from the central portion and configured toextend over and secure a native valve leaflet, and/or a chordaeengagement element extending from the support arm and configured toengage chordae of the valve site. The chordae engagement element may beconfigured to angle the chordae so that the chordae are stretched torestrict movement of the valve prosthesis in an upstream direction ofblood flow at the valve site. The chordae engagement element may beconfigured to reduce bending of the chordae to reduce stress on thechordae during the cardiac cycle.

Certain embodiments in accordance herewith are directed to valveprosthesis that may include a valve body or component includingprosthetic leaflets and a frame secured to the valve body, wherein theframe may include an inlet portion configured to engage the floor of anoutflow tract of a native heart chamber and restrict movement of theframe in a downstream direction of blood flow at a valve site and mayinclude a central portion connected to the inlet portion and configuredto fit securely within a native valve annulus. Portions of the outflowend of the frame may be flared to provide a gap between an outflow endof the frame and an outflow end of the prosthetic leaflets when theprosthetic leaflets are fully opened.

Certain embodiments in accordance herewith relate to a heart valveprosthesis that may include a tubular stent or frame and a prostheticvalve component disposed within and secured to the frame. The frame mayhave a compressed configuration for delivery within a vasculature and adeployed configuration for deployment within or adjacent a native heartvalve. In addition, at least two positioning elements or support armsmay be coupled to a distal end of the frame to position and anchor theprosthesis within the native heart valve. Each support arm may includean outer U-shaped or V-shaped support arm and/or an inner U-shaped orV-shaped support arm that both distally extend from a distal end portionof the frame when the frame is in a compressed configuration. Duringdeployment of the prosthesis, each support arm may bend radially outwardand then towards an outer surface of the frame such that it translatesmore than ninety degrees from a compressed configuration to proximallyextend from the distal end portion of the frame when the frame is in adeployed configuration.

According to another embodiment hereof, a heart valve prosthesis mayinclude a tubular stent or frame and a prosthetic valve componentdisposed within and secured to the frame. The frame may have acompressed configuration for delivery within a vasculature and adeployed configuration for deployment within a native heart valve. Inaddition, at least two positioning elements or support arms may becoupled to a distal end portion of the frame to position and anchor theprosthesis within the native heart valve. Each support arm may beattached to the frame by two V-shaped connectors such that there arefour connection points between each support arm and the frame. Eachsupport arm may include a U-shaped or V-shaped support and may beapproximately parallel with a longitudinal axis of the frame and maydistally extend from a distal end portion of the frame when the frame isin a compressed configuration. During deployment of the prosthesis, eachsupport arm may bend radially outward and then towards an outer surfaceof the frame such that the support arm translates between 135 degreesand 180 degrees from a compressed configuration to proximally extendfrom the distal end portion of the frame when the frame is in a deployedconfiguration.

Certain embodiments in accordance herewith relate to a method ofpercutaneously delivering and deploying a prosthetic valve within anative mitral valve. A prosthetic valve delivery system may be trackedthrough the vasculature to a native heart valve. The prosthetic valvedelivery system may include a valve prosthesis having a tubular stent orframe, a prosthetic valve component disposed within and secured to theframe, and/or at least two positioning elements or support arms coupledto a distal end portion of the frame, the two support arms may each havean outer U-shaped or V-shaped support arm and/or an inner U-shaped orV-shaped support arm that may both distally extend from the distal endportion of the frame when the frame is in a compressed configuration fordelivery. An outer sheath of the prosthetic valve delivery system may beretracted to expose the support arms, wherein each support arm may bendradially outward and then towards an outer surface of the frame suchthat it translates more than ninety degrees from the compressedconfiguration to proximally extend from a distal end portion of theframe and press against and/or trap a native heart valve portion and/ora heart structure in order to position the valve prosthesis. The outersheath may be further retracted to expose the frame, thereby allowing aself-expandable frame portion to self-expand into a deployedconfiguration.

BRIEF DESCRIPTION OF DRAWINGS

The foregoing and other features and advantages of the invention will beapparent from the following description of embodiments thereof asillustrated in the accompanying drawings. The accompanying drawings,which are incorporated herein and form a part of the specification,further serve to explain the principles of the invention and to enable aperson skilled in the pertinent art to make and use the invention. Thedrawings are not to scale.

FIG. 1 is a perspective sectional view of a heart that depicts a mitralvalve and various structural features related thereto.

FIG. 1A is a superior view of the mitral valve shown in FIG. 1 isolatedfrom the surrounding heart structure.

FIG. 2 is a side view of a mitral valve prosthesis in accordance with anembodiment hereof shown in a deployed configuration.

FIG. 2A is a top view of an inflow area of the mitral valve prosthesisof FIG. 2 taken in the direction of line A-A therein.

FIG. 3 is a side view of a frame of the mitral valve prosthesis of FIG.2.

FIG. 3A is a top or inflow view of the frame of FIG. 3 taken in thedirection of line A-A therein.

FIG. 3B is a cross-sectional view of a strut of the frame of FIG. 3taken in the direction of line B-B in FIG. 3A.

FIG. 4 is a side view of the frame of FIG. 3 rotated 90° about alongitudinal axis L_(A) thereof from the orientation shown in FIG. 3.

FIG. 4A is a sectional view of the frame of FIG. 4 taken along line A-Atherein.

FIG. 4B is a cross-sectional view of a strut of the frame of FIG. 4Ataken along line B-B therein.

FIGS. 5A and 5C are schematic side views, respectively, of a valveprosthesis having support arms or positioning elements according to anembodiment hereof, wherein the valve prosthesis is in a delivery orcompressed configuration with the support arms or positioning elementsdistally extending from a distal end of the prosthesis.

FIGS. 5B and 5D are schematic side views, respectively, of the valveprosthesis as shown in FIGS. 5A and 5C, wherein the valve prosthesis isin an expanded or deployed configuration with the support arms orpositioning elements proximally extending from a distal end of theprosthesis.

FIG. 6 depicts a patterned tube for forming the frame of FIGS. 3, 3A, 4and 4A laid flat for illustrative purposes.

FIG. 6A is a cross-sectional view of the patterned tube of FIG. 6 takenalong line A-A therein.

FIG. 7 is a top view of an inflow area of a frame in accordance with theembodiment of FIGS. 3, 3A, 4 and 4A.

FIG. 7A is an enlarged view of an encircled area A of FIG. 7.

FIG. 8 is a side view of a frame in accordance with the embodiment ofFIGS. 3, 3A, 4 and 4A.

FIG. 9 is a side view of a frame in accordance with another embodimenthereof.

FIG. 9A is a top view of an inflow area of the frame of FIG. 9 taken inthe direction of line A-A therein.

FIG. 9B is a cross-sectional view of a strut of the frame of FIG. 9taken along line B-B therein.

FIG. 10 depicts a patterned tube for forming the frame of FIGS. 9 and 9Alaid flat for illustrative purposes.

FIG. 10A is a cross-sectional view of the patterned tube of FIG. 10taken along line A-A therein.

FIG. 11 depicts an implanted mitral valve prosthesis in accordance withan embodiment hereof.

FIG. 12 shows an inflow portion of the frame of FIGS. 9 and 9A afterimplantation.

FIG. 13 shows the post-implantation inflow portion of the frame shown inFIG. 12 transposed on a pre-implantation inflow portion of the frame asshown in FIG. 9A.

FIG. 14 is a side view of a simplified drawing of a heart valveprosthesis in accordance with an embodiment hereof implanted within amitral valve annulus.

FIG. 15 is a cross-sectional view of a frame in accordance with anembodiment hereof.

FIG. 16 is a front or side view of a frame in accordance with anembodiment hereof.

FIGS. 16A and 16B depict front or side views of the frame of FIG. 16implanted in a native mitral valve site.

FIG. 17 is a front or side view of a valve prosthesis in accordance withan embodiment hereof.

FIG. 17A is a top or inflow view of the valve prosthesis of FIG. 17taken in the direction of line A-A therein.

FIG. 18 is a front or side view of a frame for a valve prosthesis inaccordance with an embodiment hereof.

FIG. 18A is a top or inflow view of a valve prosthesis utilizing theframe of FIG. 18 taken in the direction of line A-A therein.

FIGS. 18B and 18C depict front or side views of the valve prosthesis ofFIG. 18A implanted in a native valve site.

FIGS. 18D and 18E are front or side views of a frame for a valveprosthesis in accordance with other embodiments hereof.

FIG. 19 is an outflow or bottom front perspective view of a valveprosthesis in an open position in accordance with an embodiment hereof.

FIG. 19A illustrates an outflow or bottom front perspective view of thevalve prosthesis of FIG. 19 in a closed position.

FIG. 20 is an outflow or bottom front perspective view of a valveprosthesis in an open position in accordance with an embodiment hereof.

FIG. 20A is an outflow or bottom view of the valve prosthesis of FIG. 20taken in the direction of line A-A therein.

FIG. 21 is an outflow or bottom front perspective view of a valveprosthesis in an open position in accordance with an embodiment hereof.

FIG. 21A is an outflow or bottom view of the valve prosthesis of FIG. 21taken in the direction of line A-A therein.

FIG. 22A depicts a patterned tube for forming a frame in accordance withan embodiment hereof laid flat for illustrative purposes.

FIG. 22B depicts a saddle shape formed when the frame of FIG. 22A isexpanded.

FIG. 23 is a front or side view of a frame in accordance with anembodiment hereof.

FIG. 23A is a top or inflow view of the frame of FIG. 23 taken in thedirection of line A-A therein.

FIG. 24 illustrates a simplified drawing of a portion of a frame inaccordance with an embodiment hereof.

FIG. 25 is a side view of an enlarged portion of the valve prosthesis ofFIG. 5A, wherein a support arm is coupled to the frame at fourconnection points.

FIG. 25A is a cross-sectional view taken along line A-A of FIG. 25.

FIGS. 26A-26F illustrates various configurations of generally U-shapedor V-shaped support arms according to embodiments hereof.

FIG. 27A and FIG. 27C are schematic side and top views, respectively, ofa valve prosthesis having support arms with outer and inner U-shapedsupport arms according to an embodiment hereof, wherein the valveprosthesis is in a delivery or compressed configuration with positioningelements distally extending from a distal end of the prosthesis.

FIG. 27B and FIG. 27D are schematic side and top views, respectively, ofthe valve prosthesis of FIG. 27A and FIG. 27C, wherein the valveprosthesis is in an expanded or deployed configuration with positioningelements proximally extending from a distal end of the prosthesis.

FIGS. 28A and 28B illustrate two side views of a valve prosthesis havingouter and inner U-shaped support arms according to an embodiment hereof,wherein the support arms extend from distalmost crowns of the valveprosthesis and the valve prosthesis is in an expanded or deployedconfiguration.

FIG. 28C is an enlarged view of a portion of the valve prosthesis ofFIG. 28A.

FIGS. 29A and 29B illustrate two side views of a valve prosthesis havingouter and inner U-shaped support arms according to an embodiment hereof,wherein the support arms extend from between the distalmost crowns ofthe valve prosthesis and the valve prosthesis is in an expanded ordeployed configuration.

FIG. 29C is an enlarged view of a portion of the valve prosthesis ofFIG. 29A.

FIG. 30A is a side view of a valve prosthesis having positioningelements with triple U-shaped support arms according to an embodimenthereof, wherein the valve prosthesis is in an expanded or deployedconfiguration.

FIG. 30B is an enlarged view of a portion of the valve prosthesis ofFIG. 30A.

FIG. 31 illustrates a valve prosthesis in accordance with an embodimenthereof.

FIGS. 32A and 32B illustrate views of a valve prosthesis in accordancewith an embodiment hereof.

FIGS. 33A and 33B illustrate views of a valve prosthesis in accordancewith an embodiment hereof.

FIGS. 34A and 34B illustrate views of a valve prosthesis in accordancewith an embodiment hereof.

FIG. 35 illustrates a valve prosthesis in accordance with the embodimentof FIGS. 34A and 34B.

FIGS. 36A and 36B illustrate views of a valve prosthesis in accordancewith an embodiment hereof.

FIGS. 37A and 37B illustrate views of a valve prosthesis in accordancewith an embodiment hereof.

FIGS. 38A and 38B illustrate views of a valve prosthesis in accordancewith an embodiment hereof.

FIGS. 39A and 39B illustrate views of a valve prosthesis in accordancewith an embodiment hereof.

FIGS. 40A and 40B illustrate views of a valve prosthesis in accordancewith an embodiment hereof.

FIG. 41 illustrates a valve prosthesis in accordance with an embodimenthereof.

FIGS. 42A and 42B illustrate a valve prosthesis in accordance with anembodiment hereof.

FIG. 43 illustrates a valve prosthesis in accordance with an embodimenthereof.

FIG. 44 is a side view of a valve prosthesis in accordance with anembodiment hereof in an expanded or deployed configuration, before beingloaded into and after release from its compressed configuration within adelivery system as shown in FIGS. 44A and 44B.

FIGS. 44A and 44B are side and end views, respectively, of the valveprosthesis of FIG. 44 in an unexpanded or delivery or compressedconfiguration, loaded into a delivery system in accordance with anembodiment hereof.

FIGS. 45A-45E illustrate side views of the valve prosthesis of FIG. 44loaded within the delivery system of FIGS. 44A and 44B, wherein a sheathof the delivery system is progressively retracted to release the valveprosthesis therefrom.

FIGS. 46A-46E illustrate a method of implanting a valve prosthesis at amitral valve target location within a heart in accordance with anembodiment hereof.

FIG. 47 is a side view of a valve prosthesis having commissural supportarms in accordance with an embodiment hereof in an expanded or deployedconfiguration.

FIG. 47A is a side sectional view of a distal portion of a deliverysystem with the valve prosthesis of FIG. 47 in a partially deployedconfiguration, in accordance with an embodiment hereof.

FIG. 48 is a side view of a valve prosthesis having commissural anchorsin accordance with an embodiment hereof in an expanded or deployedconfiguration.

FIG. 48A is a side sectional view of a distal portion of a deliverysystem with the valve prosthesis of FIG. 48 in a partially deployedconfiguration, in accordance with an embodiment hereof.

FIG. 48B illustrates the valve prosthesis of FIG. 48 implanted at amitral valve target location within a heart in accordance with anembodiment hereof.

FIG. 49 is a side view of a valve prosthesis having cantilever elementsin accordance with an embodiment hereof in an expanded or deployedconfiguration.

FIGS. 49A and 49B illustrates the valve prosthesis of FIG. 49 implantedat a mitral valve target location within a heart in accordance with anembodiment hereof.

FIG. 50 is a side view of a valve prosthesis having inflow support armsin accordance with an embodiment hereof in an expanded or deployedconfiguration.

FIGS. 51A, 51B, 51BB, 51C, 51CC, 51D, 51DD, 51E, and 51EE illustrate amethod of implanting the valve prosthesis of FIG. 50 within a mitralvalve of a heart in accordance with an embodiment hereof.

FIG. 52 is a side view of a valve prosthesis in accordance with anembodiment hereof in a first or acute deployed configuration.

DETAILED DESCRIPTION OF THE INVENTION

Specific embodiments of the present invention are now described withreference to the figures, wherein like reference numbers indicateidentical or functionally similar elements. The terms “distal” and“proximal” are used in the following description with respect to aposition or direction relative to the treating clinician. “Distal” or“distally” are a position distant from or in a direction away from theclinician. “Proximal” and “proximally” are a position near or in adirection toward the clinician. As used herein with reference to animplanted valve prosthesis, the terms “distal”, “outlet”, and “outflow”are understood to mean downstream to the direction of blood flow, andthe terms “proximal”, “inlet”, or “inflow” are understood to meanupstream to the direction of blood flow. In addition, as used herein,the terms “outward” or “outwardly” refer to a position radially awayfrom a longitudinal axis of a frame of the valve prosthesis and theterms “inward” or “inwardly” refer to a position radially toward alongitudinal axis of the frame of the valve prosthesis. As well theterms “backward” or “backwardly” refer to the relative transition from adownstream position to an upstream position and the terms “forward” or“forwardly” refer to the relative transition from an upstream positionto a downstream position.

The following detailed description is merely exemplary in nature and isnot intended to limit the invention or the application and uses of theinvention. Although the description of embodiments hereof are in thecontext of treatment of heart valves and particularly a mitral valve,the invention may also be adapted for use in other valve replacementprocedures where it is deemed useful. Furthermore, there is no intentionto be bound by any expressed or implied theory presented in thepreceding technical field, background, brief summary or the followingdetailed description.

FIG. 1 is a perspective sectional view of a heart (H) that depicts amitral valve (MV) and various structural features related thereto, withFIG. 1A being a superior view of the mitral valve isolated fromsurrounding heart structure. The mitral valve is found between the leftatrium (not shown) and the left ventricle (LV) and is surrounded by andattached to a fibrous atrioventricular ring of the heart that may bemore commonly referred to as the mitral valve annulus (MVA). As bestshown in FIG. 1A, the mitral valve annulus may be considered to have aD-shape rather than being circular or elliptical. The mitral valveincludes anterior and posterior leaflets (AL, PL) that open duringdiastole to allow blood flow from the left atrium to the left ventricle.During ventricular systole, the anterior and posterior leaflets close toprevent backflow to the left atrium while the mitral valve annuluscontracts and reduces its surface area to help provide complete closureof the leaflets. The anterior and posterior leaflets are attached topapillary muscles (PM) within the left ventricle by way of the chordaetendinae (CT), which are strong, fibrous strings attached to theleaflets of the heart on the ventricular side. When the anterior andposterior leaflets of the mitral valve close, the chordae tendinae aretensioned to prevent the leaflets from swinging back into the atriumcavity.

Due to the unique shape of a native mitral valve and the functionalityof the structure associated therewith that can cause axial movement of aprosthetic mitral valve during the cardiac cycle, i.e., axial movementthat may be caused by the cyclic tensioning of the chordae tendinaeand/or contraction of the D-shaped mitral valve annulus duringventricular systole, a mitral valve prosthesis according to embodimentshereof includes a frame having a flexible, anatomically conforminginflow portion that is designed to maintain sealing with the atrialsurface surrounding the mitral valve during the cardiac cycle. In orderto ensure circumferential sealing of a mitral valve prosthesis to theheart, the inflow portion of the prosthesis may comprise a largerdiameter than the largest diameter of the native mitral valve annulus.

FIG. 2 is a side view of a heart or mitral valve prosthesis 200 inaccordance with an embodiment hereof shown in a deployed configuration,with FIG. 2A being a top view of an inflow area of heart valveprosthesis 200 taken in the direction of line A-A in FIG. 2. Heart valveprosthesis 200 includes a valve body or component 220 attached within aninterior of a frame or support structure 210, which also may beconsidered a stent or stent-like framework or structure. Frame 210 hasan inflow portion 202 that may be described as having a hyperparabolicor saddle shape or profile such that the inflow end of frame 210 isnon-planar. Stated another way, diametrically-opposed lateral portionsof a peripheral or radial edge of inflow portion 202 curve downward fromraised diametrically-opposed central portions of the peripheral orradial edge of inflow portion 202. A normal, non-diseased native mitralvalve annulus has a hyperparabolic or saddle shape. In an embodiment,inflow portion 202 may comprise a hyperparabolic or saddle shape thatmatches, corresponds to or is similar to the saddle shape of a nativemitral valve annulus. In an embodiment, valve component 220 is a one-waybicuspid replacement valve having first and second prosthetic valveleaflets 224A, 224B, which is capable of blocking flow in one directionto regulate flow therethrough. In embodiments hereof, prosthetic valvecomponents may include valve leaflets to form a bicuspid, tricuspid, ortubular replacement valve, each of which is capable of blocking flow inone direction to regulate flow therethrough. Valve component 220 and/orvalve leaflets 224A, 224B thereof are sutured or otherwise securely andsealingly attached to an interior surface of frame 210 and/or to graftmaterial 226, which encloses or lines various portions of frame 210 aswould be known to one of ordinary skill in the art of prosthetic tissuevalve construction. In embodiments in accordance herewith and asdescribed in more detail herein, graft material 226 secured to frame 210within an inflow area of prosthesis 200 aids in sealing. Graft material226 may comprise one or more pieces of material, such as a single skirtof material, attached or coupled, such as sewn, to an inner portion ofthe frame, one or more pieces of material, such as a single skirt ofmaterial, attached or coupled, such as sewn, to an outer portion of theframe, one or more pieces of material, such as a two-layer skirt ofmaterial, attached or coupled, such as sewn, to both an inner portion ofthe frame and/or an outer portion of the frame and/or any combinationthereof. The graft material and/or skirts may be designed for differentapplications or uses. For example, an inner skirt material may be chosenso as to be impermeable to blood flow or other factors while an outerskirt material may be chosen so as to interact with heart tissue in amanner that may encourage cellular or tissue growth within and/or on thematerial and/or may prevent the passage of blood between the valveprosthesis and heart tissue. Graft material 226 secured to frame 210proximate an outflow area of prosthesis 200 may provide a chordaeengagement member, which may comprise a tent-like or hammock-likestructure 228. The chordae engagement member may function to reduce oreliminate relative motion between frame 210 and the chordae tendinaewhen prosthesis 200 is implanted within a native mitral valve.

FIGS. 3, 3A, 4 and 4A illustrate frame 210 in a deployed configurationremoved from a remainder of prosthesis 200. FIGS. 3 and 4 are side viewsof frame 210, with FIG. 4 showing frame 210 rotated 90° about alongitudinal axis L_(A) thereof from the orientation shown in FIG. 3.FIG. 3A is a top or inflow view of frame 210 taken in the direction ofline A-A in FIG. 3 and FIG. 3B is a cross-sectional view of a strut 512Bof frame 210 taken along line B-B in FIG. 3A. FIG. 4A is a sectionalview of frame 210 taken along line A-A in FIG. 4 and FIG. 4B is across-sectional view of strut 512B of frame 210 taken along line B-B inFIG. 4A.

Frame 210 may be a unitary structure that defines a proximal or inflowportion 202, a central or valve-retaining tubular portion 204 and a pairof support arms or positioning elements 206A, 206B. In some embodimentshereof, proximal or inflow portion 202 may be considered an atrialsegment of valve prosthesis 200 and central or valve-retaining tubularportion 204 may be considered a ventricular or annulus segment of valveprosthesis 200 without departing from the scope hereof. In the deployedconfiguration of frame 210, inflow portion 202 outwardly extends from afirst, proximal or inflow end 203 of valve-retaining tubular portion 204and support arms 206A, 206B backwardly extend from circumferentiallyspaced apart locations of an opposing second, distal or outflow end 205of valve-retaining tubular portion 204. When prosthesis 200 is implantedwithin a native mitral valve, inflow portion 202 of frame 210 isconfigured to engage an area of the left atrium that surrounds thenative mitral valve, valve-retaining tubular portion 204 of frame 210 isconfigured to axially extend through the native mitral valve and thuslysituates valve component 220 within the mitral valve annulus, andsupport arms 206A, 206B are configured to capture respective valveleaflets of the mitral valve and to secure them within the leftventricle without obstructing the outflow area of prosthesis 200 or theleft ventricular outflow tract. Leaflets of a valve component (notshown) may attach to upstream crowns 213 of valve-retaining tubularportion 204 to extend into atrial or inflow portion 202 (and into theleft atrium when in situ) such that the valve component is not solelylocated on or within the outflow or ventricular portion 204 (and intothe left ventricle in situ). By locating a portion of the valve leafletsin the left atrium, the required length of central or valve-retainingtubular portion 204 is minimized and the length of frame 210 thatprotrudes into the left ventricle may be reduced. The operation of, andvarious alternate embodiments for, support arms 206A, 206B will bedescribed in more detail herein.

In accordance with some embodiments hereof, the frames or supportstructures for valve prosthesis in accordance herewith have a generallytubular expandable body with a stepped profile. FIGS. 5A, 5B, 5C, and 5Dshow simplified views of a frame or stent structure 310 in accordancewith an embodiment hereof having a stepped-down profile as it extendsbetween a proximal or inflow end 303 and a distal or outflow end 305,with FIGS. 5A and 5C showing alternate side views respectively of frame310 in a compressed or delivery configuration and with FIGS. 5B and 5Dshowing alternate side views respectively of frame 310 in an expanded ordeployed configuration. More particularly, FIGS. 5C and 5D are a sideview of the frame as shown in FIGS. 5A and 5B rotated 90° about alongitudinal axis L_(A) thereof from the orientation shown in FIGS. 5Aand 5B. Frame 310 includes a central or ventricular segment 304 havingan expanded diameter Dv and a proximal, inflow or atrial segment 302having an expanded diameter DA which is greater than diameter Dv. Whenplaced at a native mitral valve target site, central or ventricularsegment 304 extends into the left ventricle and inflow or atrial segment302 extends into the left atrium. Each segment of frame or stent 310,i.e., central segment 304 and/or inflow segment 302, may be designedwith a number of different configurations and sizes to meet thedifferent requirements of the locations in which it may be implanted. Aswell each segment of frame or stent 310, i.e., central segment 304and/or inflow segment 302, may have the same or different cross-sectionwhich may be for example circular, ellipsoidal, rectangular, hexagonal,square, or other polygonal shape.

Frames or support structures in accordance with some embodiments hereofmay be a unitary integral structure formed from a single tubularcomponent and, although not shown in detail in the embodiment of FIGS.5A-5D, include a lattice or stent-like configuration that may beproduced by machining or laser cutting the design from a metal tube, asis commonly employed in the manufacturing of stents. Any frame for valveprosthesis in accordance with embodiments hereof may be laser cut from asolid tubular component of a self-expanding material such that the stentis an integral, one-piece structure that does not include separatecomponents that are joined together. A single integral structure allowsthe frame to be crimped or compressed to a low delivery profile.Alternatively, rather than being laser cut, frames in accordance withembodiments hereof may be formed using any of a number of differentmethods that would be apparent to one of ordinary skill in the art suchas connecting individual elements together, such as annular stentstruts, chemical etching, or another method of forming a desired shapefrom a solid component.

In one method of forming a frame in accordance herewith, and moreparticularly in an initial step in manufacturing frame 210, a tube 510of a suitable material is etched, cut or otherwise machined to have thepattern depicted in FIG. 6. FIG. 6 depicts for illustrative purposesonly patterned tube 510 laid flat so that the cut structures of inflowportion 202, valve-retaining tubular portion 204 and support arms 206A,206B may be more readily identified and described. Valve-retainingtubular portion 204 has a stent-like framework that definesdiamond-shaped openings 518 and a series of upstream valleys 514A anddownstream valleys 514B. Support arms 206A, 206B are formed from innerand outer looped struts 513, 515 with the outer looped struts 515forming outer support arms extending from spaced apart valleys 514B ofvalve-retaining tubular portion 204 and with the inner looped struts 513forming inner support arms extending from spaced apart downstream peaks,crowns or apexes 517 of valve-retaining tubular portion 204. In anotherembodiment in accordance herewith, tube 510 may be cut into a patternsuch that frame 210 is formed to have one or more support arms asdescribed with reference to any of the other embodiments herein.

In one embodiment, inflow portion 202 is formed from a plurality ofstruts 512 having a cut width We that may be less than a thickness Tthereof, as shown in FIG. 6A which is a cross-sectional view of strut512B taken along line A-A in FIG. 6. Each strut 512 defines a basesegment 509 and divergent first and second branch segments 511A, 511B.Accordingly, strut 512 may be considered to have a Y-shaped cut pattern.Base segments 509 of a respective pair of struts 512, for instance basesegments 509A, 509B of struts 512A, 512B, extend from every other valley514 at inflow end 203 of valve-retaining tubular portion 204. Aplurality of crowns 513 are formed between first and second branchsegments 511A, 511B of adjacent struts 512. Crowns 513 form radiallyoutward ends of inflow portion 202 of frame 210, as shown in FIG. 3A.Circumferentially adjacent crowns 513 are not directly connected to eachother and thereby provide inflow portion 202 with flexibility. Inembodiments hereof, the geometry of the cut pattern, materialproperties, and/or the shaping processes may be selected to provideincreased or decreased flexibility and/or to improve the structuralintegrity of the prosthesis.

In one embodiment, subsequent processing steps are performed onpatterned tube 510 in order to form frame 210 in its expanded state asshown in FIGS. 3, 3A, 4 and 4A, with FIGS. 7, 7A and 8 being variousviews of a frame 210 in accordance with the embodiment of FIGS. 3, 3A, 4and 4A. In one or more processing steps, patterned tube 510 may beradially expanded to set a tubular shape and expanded diameter ofvalve-retaining tubular portion 204 that is suitable for receiving valvecomponent 220 therein. In one or more additional processing steps,support arms 206A, 206B may be rotated outward and backward relative tooutflow end 205 of valve-retaining tubular portion 204 and heat treatedto set a shape thereof. In one or more additional processing steps,struts 512 of inflow portion 202 of patterned tube 510 may be made tooutwardly extend from inflow end 203 of valve-retaining tubular portion204 and subjected to a forming process to have a substantially s-shapedprofile, as best seen in FIG. 4A. Somewhat counter-intuitively, a firstbend 416A and an opposing second bend 416B that form the substantiallys-shaped profile of strut 512 may be bent or curved over the cut widthW_(C) of the strut, as shown in FIGS. 3B and 4B, rather than being bentor curved over thickness T of the strut. First and second bends 416A,416B of s-shaped strut 512 may be able to be formed in this manner dueto one or more twisted areas TA₁, TA₂, TA₃ of strut 512 that occurduring formation of inflow portion 202. More particularly with referenceto FIGS. 3A and 4A, base segment 509 of each strut 512 may have atwisted area TA₁ near or adjacent to where the respective base segment509 outwardly extends from inflow end 203 of valve-retaining tubularportion 204. Although not intending to be bound by theory, twisted areaTA₁ turns cut width W_(C) of the respective strut 512 approximately 90degrees from the cut pattern shown in FIG. 6 such that the narrowerportion W_(C) of the respective strut 512 is subjected to the formingprocess that creates first and second bends 416A, 416B. As well withreference to FIG. 3A, first and second branch segments 511A, 511B ofeach strut 512 may have twisted areas TA₂, TA₃, respectively, near oradjacent to their respective crowns 513. Although not intending to bebound by theory, twisted areas TA₂, TA₃ turn cut width W_(C) of therespective strut 512 in a direction opposite of twisted area TA₁ toreturn cut width W_(C) to a similar orientation as shown in the cutpattern in FIG. 6, which results in cut width W_(C) facing inward andoutward along at least a portion of first and second branch segments511A, 511B of struts 512 and through crowns 513 of inflow portion 202.

In the embodiment of frame 210 shown in FIGS. 3, 3A, 4 and 4A, inflowportion 202 may be described as having a ring of alternating openings orcells C1, C2 that are formed between respective portions of struts 512and crowns 513. Cells C1, C2 have widths W₁, W₂, respectively, withwidth W₁ of cell C1 being less than width W₂ of cell C2, as best shownin FIG. 3A. Although not intending to be bound by theory, thealternating size of cells C1, C2 contributes to base segments 509 thatemanate from a common valley 514 of tubular portion 204 having twistedareas TA₁ that twist or turn away from each other, or in other wordstwist in opposite directions from each other. For example with referencethe pair of base segments 509A, 509B shown in FIGS. 3A, 7 and 7A,twisted area TA₁ of base segment 509A will turn strut 512Acounterclockwise toward its adjacent cell C2, such that twisted area TA₁of base segment 509A may be considered to have a left-hand twist, andtwisted area TA₁ of base segment 509B will turn strut 512B clockwisetoward its adjacent cell C2, such that twisted area TA₁ of base segment509B may be considered to have a right-hand twist.

In one embodiment, the s-shaped struts 512 that form inflow portion 202of frame 210 act similarly to cantilever beams when interacting with theanatomy of the heart as a supporting and sealing structure of prosthesis200. During the pressure changes and cyclical contractions of the heart,the s-shaped struts 512 are able to deflect while maintaining an axialforce against the atrial surface of the heart that is sufficient forsealing and the prevention of paravalvular leakage between the frame andtissue surface. As well the combination of twisted areas TA₁, TA₂, TA₃and s-shape of struts 512 of inflow portion 202 permit the inflow areaof prosthesis 200 to readily deflect, flex and/or move during thecardiac cycle while also maintaining sufficient axial stiffness toprovide sealing contact with the atrial surface that surrounds theimplanted prosthesis. In addition, the twisted areas TA₁, TA₂, TA₃ ofs-shaped struts 512 reduce strain and improve the structural integrityof frame 210, and more particularly the structural integrity of inflowportion 202 thereof.

FIGS. 9 and 9A are various views of a frame 810 in a deployedconfiguration in accordance with another embodiment hereof that issuitable for use in forming a valve prosthesis similar to prosthesis 200described above. FIG. 9 is a side view of frame 810, with FIG. 9A beinga top or inflow view of frame 810 taken in the direction of line A-A inFIG. 9. Frame 810 may be a unitary structure that defines an inflowportion 802, a valve-retaining tubular portion 804 and a pair of supportarms 806A, 806B. In a deployed configuration of frame 810, inflowportion 802 outwardly extends from a first or inflow end 803 ofvalve-retaining tubular portion 804 and support arms 806A, 806Bbackwardly extend from circumferentially spaced apart locations of anopposing second or outflow end 805 of valve-retaining tubular portion804. When implanted within a native mitral valve as a support structureof a mitral valve prosthesis, inflow portion 802 is configured to engagean area of the left atrium that surrounds the native mitral valve,valve-retaining tubular portion 804 is configured to axially extendthrough the native mitral valve and thusly situates a prosthetic valvecomponent within the mitral valve annulus, and support arms 806A, 806Bare configured to capture respective valve leaflets of the mitral valveand to secure them within the left ventricle without obstructing theoutflow area of the prosthetic valve or the left ventricular outflowtract.

In one embodiment, in an initial step in manufacturing frame 810, a tube910 of a suitable material is etched, cut or otherwise machined to havethe pattern depicted in FIG. 10. FIG. 10 depicts for illustrativepurposes only patterned tube 910 laid flat so that the cut structures ofinflow portion 802, valve-retaining tubular portion 804 and support arms806A, 806B may be more readily identified and described. Valve-retainingtubular portion 804 may have a stent-like framework that definesdiamond-shaped openings 918 and a series of upstream nodes or valleys914A and downstream nodes or valleys 914B. Each support arm 806A, 806Bmay be formed to have inner side struts 913A, 913B and an outer loopedstrut 915. Outer looped struts 915 may form outer support arms thatextend from spaced apart downstream crown or peaks 917B ofvalve-retaining tubular portion 804 and inner side struts 913A, 913B mayform chordae engagement, guiding and/or tensioning elements, asdescribed in more detail below, that extend from respective downstreamvalleys 914B within their respective outer looped strut 915 and connecttherewith at opposing interior locations 919A, 919B. In anotherembodiment in accordance herewith, tube 910 may be cut into a patternsuch that frame 810 is formed to have support arms as described withreference to any of the other embodiments herein. In one or moreembodiments, support arms may comprise one or more outer loops and/orone or more inner loops. The inner loops may or may not be attached orcoupled to one or more of the outer loops. In one or more embodiments,support arms may be attached or coupled at one or more frame locations.For example, the support arms may be attached or coupled to the frame atone or more points at either an outflow crown 917B, a node 914B, and/oralong a strut connecting an outflow crown and a node. The support armsmay be attached or coupled at one or more points located around thecircumference of an outflow or distal portion of the frame.

In one embodiment, inflow portion 802 may be formed from a plurality ofstruts 912 having a cut width We that is less than a thickness Tthereof, as shown in FIG. 10A which is a cross-sectional view of a strut912 taken along line A-A in FIG. 10. Each strut 912 may define a basesegment 909 and first and second branch segments 911A, 911B, whichdiverge from base segment 909 at a respective node 921. Accordingly,strut 912 may be considered to have a Y-shaped cut pattern. A basesegment 909 of a respective strut 912 extends from every upstream valley914A at inflow end 803 of valve-retaining tubular portion 804. Each basesegment 909 has a length that disposes a respective node 921 of strut912 upstream of upstream peaks 917A. In an embodiment, base segment 909has a length such that node 921 of strut 912 is disposed upstream ofupstream peaks 917A by at least half a length of the base segment.Crowns 913 are formed between first and second branch segments 911A,911B of adjacent struts 912. Crowns 913 may form radially outward endsof inflow portion 902 of frame 910, as shown in FIG. 9A.Circumferentially adjacent crowns 913 may not be directly connected toeach other and thereby provide inflow portion 802 with improvedflexibility.

In one embodiment, subsequent processing steps are performed onpatterned tube 910 in order to form expanded frame 810 as shown in FIGS.9 and 9A. In one or more processing steps, patterned tube 910 may beradially expanded to set a tubular shape and diameter of valve-retainingtubular portion 804 that is suitable for receiving a prosthetic valvecomponent therein. In one or more additional processing steps, supportarms 806A, 806B may be rotated outward and backward relative to outflowend 805 of valve-retaining tubular portion 804 and heat treated to set ashape thereof. In one or more additional processing steps, struts 912 ofinflow portion 802 of patterned tube 910 may be made to outwardly extendfrom inflow end 803 of valve-retaining tubular portion 804 and subjectedto a forming process to have a substantially s-shaped profile, as bestseen in FIG. 9. Somewhat counter-intuitively, a first bend 816A and anopposing second bend 816B that form the substantially s-shaped profileof strut 912 may be bent or curved over the cut width W_(C) of thestrut, as shown in FIG. 9B, rather than being bent or curved overthickness T of the strut. First and second bends 816A, 816B of s-shapedstrut 912 are able to be formed in this manner due to one or moretwisted areas TA₁, TA₂, TA₃ of strut 912 that occur during formation ofinflow portion 802. More particularly with reference to FIG. 9A, basesegment 909 of each strut 912 may have a twisted area TA₁ near oradjacent to where the respective base segment 909 outwardly extends frominflow end 803 of valve-retaining tubular portion 804. Although notintending to be bound by theory, twisted area TA₁ turns cut width W_(C)of the respective strut 912 approximately 90 degrees from the cutpattern shown in FIG. 10 such that the wider thickness T of therespective strut 912 is subjected to the forming process that createsfirst and second bends 816A, 816B. As well with reference to FIG. 9A,first and second branch segments 911A, 911B of each strut 912 havetwisted areas TA₂, TA₃, respectively, near or adjacent to theirrespective crowns 913. Although not intending to be bound by theory,twisted areas TA₂, TA₃ turn cut width W_(C) of the respective strut 912in a direction opposite of twisted area TA₁ to return cut width W_(C) toa similar orientation as shown in the cut pattern in FIG. 10, whichresults in cut width W_(C) facing inward and outward along at least aportion of first and second branch segments 911A, 911B of struts 912 andthrough crowns 913 of inflow portion 802.

In the embodiment of frame 810 shown in FIGS. 9 and 9A, inflow portion802 may be described as having a ring of equal or like sized and shapedcells C1 that are formed between respective portions of struts 912 andcrowns 913. In contrast to the radial symmetric appearance of cells C1,C2 of inflow portion 202 of frame 210 shown in FIG. 3A, cells C1 ofinflow portion 802 of frame 810 shown in FIG. 9A appear to spiralclockwise, exhibiting cyclic symmetry. Although not intending to bebound by theory, the spiral design of the inflow portion 802 results inthe struts 912 having twisted areas TA₁ that twist or turn in a commonor same direction from valve-retaining tubular section 804. In theembodiment shown in FIGS. 9 and 9A, the twisted area TA₁ of each basesegment 909 turns the respective strut 912 clockwise relative to inflowend 803 of valve-retaining portion 804 such that twisted area TA₁ may beconsidered to have a right-hand twist. In another embodiment (notshown), the twisted area TA₁ of each base segment 909 turns therespective strut 912 counterclockwise relative to inflow end 803 ofvalve-retaining portion 804 such that twisted area TA₁ may be consideredto have a left-hand twist.

With reference to FIG. 9, first bend 816A of each s-shaped strut 912 hasan apex 822 that is longitudinally disposed at or near downstreamvalleys 914B of valve-retaining tubular portion 804. The increased depthof first bend 816A and the corresponding increased height of second bend816B, as compared to first and second bends 816A, 816B, respectively,are made possible by the longer length of inflow struts 912 relative toan axial length of valve-retaining tubular portion 804 as compared to alength of inflow struts 512 relative to an axial length ofvalve-retaining tubular portion 204. In another embodiment, apex 822 offirst bend 816A may be positioned at or near upstream valleys 914A ofvalve-retaining tubular portion 804, similar to the location of apex 422of first bend 416A as shown in FIGS. 4 and 8. In other embodiments inaccordance herewith, apex 822 of s-shaped struts 912 and apex 422 ofs-shaped struts 512 may be suitably disposed anywhere along the axiallength of valve-retaining tubular portions 204, 804, respectively, inorder to tailor the flexibility of the respective inlet portion 202, 802for a particular application.

In some embodiments, the s-shaped struts 912 that form inflow portion802 of frame 810 act similarly to cantilever beams when interacting withthe anatomy of the heart as a supporting and sealing structure of avalve prosthesis in accordance with embodiments hereof. During thepressure changes and cyclical contractions of the heart, the s-shapedstruts 912 are able to deflect while maintaining an axial force againsta surface of the heart such as an atrial surface that is sufficient forsealing and the prevention of paravalvular leakage between the frame andtissue surface. As well the combination of twisted areas TA₁, TA₂, TA₃and the s-shape of struts 912 of inflow portion 802 may permit theinflow area of the valve prosthesis in accordance with embodimentshereof to readily deflect, flex and/or move during the cardiac cyclewhile also maintaining sufficient axial stiffness to provide sealingcontact with the tissue surface that surrounds the implanted prosthesis.In addition, the twisted areas TA₁, TA₂, TA₃ of s-shaped struts 912reduce strain and improve the structural integrity of frame 810, andmore particularly the structural integrity of inflow portion 802thereof. Another benefit of the design of inflow portion 802 of frame810 is that it may readily conform to the D-shape of the mitral valveannulus by allowing deflection or movement in a radial direction DR ofstruts 912 and the cells C1 defined thereby, as shown in FIGS. 11-13.FIG. 11 shows an implanted mitral valve prosthesis having a frame 810that shows how individual struts 912 have radially deflected or movedafter implantation to “lay down” a bit flatter and conform to theD-shape of the native mitral valve annulus. This anatomically conformingfeature of frame 810 is more clearly depicted in FIGS. 12 and 13, withFIG. 12 showing the deformation of inflow portion 802 of frame 810 afterimplantation and with FIG. 13 showing the post-implantation deformedinflow portion 802 of FIG. 12 transposed on a pre-implantation inflowportion 802 of FIG. 9A

FIG. 14 is a side view of a simplified drawing of a heart valveprosthesis 1400 in accordance with an embodiment hereof implanted withina mitral valve annulus (MVA) of a mitral valve (MV). Valve prosthesis1400 is configured to be implanted in mitral valve annulus (MVA) toreplace the function of the native mitral valve (MV). In otherembodiments, valve prosthesis 1400, as well as other valve prosthesisdisclosed herein, may be adapted for placement within another of thenative heart valves, such as the aortic, pulmonary, or tricuspid heartvalve, and the actual shape and configuration of the valve prosthesiscan depend upon the native heart valve being replaced.

Heart valve prosthesis 1400 may include a frame 1410 that supports aprosthetic valve body or component (not shown). An outflow or distalportion of frame 1410 corresponds to a distal or outflow end 1405 ofvalve prosthesis 1400 and an opposite end of frame 1410 defines aninflow or proximal portion corresponding to a proximal or inflow end1403 of valve prosthesis 1400. As noted above the terms “distal” or“outflow” are understood to mean downstream to the direction of bloodflow BF and the terms “proximal” or “inflow” are understood to meanupstream to the direction of blood flow.

Frame 1410 may include a pair of support arms 1406 extending from acentral or valve-retaining tubular portion 1404 of frame 1410 andconfigured to extend over and secure the native leaflet (AL, PL). In oneembodiment, upon implantation, each support arm 1406 is configured toengage, capture, clamp and/or immobilize a corresponding leaflet (AL,PL) of the mitral valve (MV), and hold the leaflet close to centralportion 1404. In some embodiments, one or more support arms may engage,capture, clamp, and/or immobilize one or more chordae tendinae eitherdirectly or indirectly. In other embodiments, frame 1410 may includemultiple support arms 1406 with each support arm 1406 corresponding to aseparate native leaflet of the heart valve within which the heart valveprosthesis is to be implanted. In embodiments hereof, proper seating ofthe valve prosthesis within the annulus of a native heart valve can beachieved by capturing one or more native leaflets with the support armsof the frame. For instance, a radial and/or axial force generated by thevalve prosthesis 1410 in the atrium (AF, AW) against support arms 1406can create a “sandwich effect,” which in some embodiments can seat valveprosthesis 1410 by capturing or pinching leaflets (AL, PL) and atrialtissue against central portion 1404.

In embodiments hereof, support arms 1406 may be sized or shaped totension the chordae tendinae (CT). As noted above, the chordae tendinaeconnect to the native valve leaflets (AL, PL) and can act like “tierods” in an engineering sense. In some patients, not only do the chordaetendinae (CT) help prevent prolapse of the native valve leaflets duringsystole, they also help support the left ventricular muscle massthroughout the cardiac cycle. In embodiments in accordance herewith, thetension between the chordae tendinae (CT) and the native valve leaflets(AL, PL) can serve to prevent frame 1410 from moving or migrating, forexample lifting into the patient's atrium. In some embodiments, thechordae tension can serve to substantially prevent paravalvular leakage.For example, one or more support arms that interact with chordae maycreate adequate tension in the chordae to deform the inflow portion ofthe valve prosthesis against the floor of the atrium but at forces lowenough to prevent tensile failure of the chordae. To preserve thiseffect over time, the support arms that engage or interact with thechordae must prevent abrasion of the chordae. One method to preventabrasion of the chordae is by eliminating or diminishing any relativemotion between the chordae and the support arm, either by promotingtissue ingrowth, converting the relative motion to tension, and/oractively clamping the chordae. In one embodiment, a support arm couldavoid or minimize the number of chordae it interacts with throughgeometric design. In one embodiment, a support arm may be designed tomove with the chordae, either by absorbing the relative motion in theform of deformation or by transferring the relative motion to adifferent part of the valve prosthesis. In one embodiment, the relativemotion between a support arm and the chordae may be allowed, but thefriction between the support arm and chordae could be minimized to thepoint where abrasion is insignificant or not a concern. In someembodiments, paravalvular leakage can be substantially prevented bypositioning a sealing member or surface of the valve prosthesis 1400between inflow end 1403 and outflow end 1405.

In embodiments hereof, support arms 1406 may be sized or shaped toincrease valve stability. Support arms 1406 may, for example, serve tosubstantially prevent the native valve leaflets (AL, PL) fromobstructing flow through outflow tract (OF). In embodiments hereof,support arms 1406 may serve to prevent the native valve leaflets (AL,PL) from interacting with prosthetic leaflets of valve prosthesis 1410.In embodiments hereof, support arms 1406 may position the native valveleaflets (AL, PL) to minimizing paravalvular leaks and/or maintainproper alignment of the valve prosthesis. In embodiments hereof, supportarms 1406 may serve to avoid systolic anterior mobility and/or maintainvalve stability by preventing migration of the valve prosthesis into theatrium or ventricle. In embodiments hereof, support arms 1406 may beconfigured to enhance overall frame strength.

In embodiments hereof, frame 1410 may include an inlet portion 1402configured to engage the atrial floor (AF) of the outflow tract of thenative heart atrium. In embodiments hereof, inlet portion 1402 mayrestrict movement of valve prosthesis 1400 in a downstream direction ofblood flow BF at the valve site. In embodiments hereof, inlet portion1402 of frame 1410 may be configured to deform the atrial floor (AF) ofthe outflow tract in an upstream direction of blood flow BF at the valvesite. For example, a “sandwich force” may be created between the inflowor inlet portion of the frame 1402 and the outflow or outlet portion1404 of the frame 1405. This force can either deflect the inflow portionof the frame 1402 against the atrial floor AF or deform the atrial floorAF to match the contour of inflow 1402, depending upon the stiffness ofthe frame. In some embodiments, inlet portion 1402 may be sized tocontact the entirety of the atrial floor (AF) and a portion of theatrial wall (AW), with an example of such a configuration being shown inFIG. 14. In embodiments hereof, inlet portion 1402 is sized to contact asubstantial majority of the atrial floor (AF). Other suitableconfigurations can be used. In embodiments hereof, frame 1410 may have atransverse cross-section or diameter that is smaller than annulus (MVA).In some embodiments, such a configuration can serve to prevent radialforce on frame 1410 from annulus (MVA), which can serve to maintain adesired shape of a prosthetic valve body or component supported withinframe 1410.

Because valve prosthesis 1400 may be used in a portion of the body thatundergoes substantial movement, it may be desirable for one or moreportions of valve prosthesis 1400, such as frame 1410 to be flexible.For example, in some embodiments, at least a portion of inlet portion1402 may have a flexibility from about 0.8 N/m to about 2 N/m. Inembodiments hereof, at least a portion of inlet portion 1402 may have aflexibility of about 1.25 N/m. In some embodiments hereof, inlet portion1402 may include one or more diamond-shaped cells. In some embodimentshereof, inlet portion 1402 may be formed of twisted strands of nitinolas previously discussed above.

Central portion 1404 of frame 1410 may be configured to conform to aheart valve annulus. In embodiments hereof, such a configuration canhelp anchor valve prosthesis 1400 within an annulus to prevent lateralmovement or migration of valve prosthesis 1400 due to the normalmovement during the cardiac cycle of the heart. In embodiments hereof,central portion 1404 may be shaped to adapt to the specific anatomy ofan individual. For example, in some embodiments, central portion 1404 isconfigured to flex and deform so as to mimic a natural cardiac movementof the heart through the cardiac cycle. In other embodiments, centralportion 1404 may be substantially rigid to avoid flexing or deformationduring the cardiac cycle. In further embodiments, central portion 1404may be sized to be smaller than the native annulus, avoiding deformationof the central portion due to the interaction with the native annulus.

The shape of central portion 1404 may be configured to reduce the riskof valve prosthesis migration and paravalvular leakage. In embodimentshereof, a transverse cross-section of central portion 1404 may define asubstantially circular, oval, elliptical or another geometric ornon-geometric shape, such as D-shaped, while a longitudinal profile ofcentral portion 1404 may define any desirable geometric or non-geometricshape. In other embodiments hereof, central portion 1404 may be formedto have a substantially straight profile, for example, beingsubstantially cylindrical and parallel to a longitudinal axis L_(A) offrame 1410. Central portion 1404 may have one or more flared portions,for example, diverging away from a longitudinal axis L_(A) of frame1410.

In some embodiments, central portion 1404 may have a transversecross-section or diameter that is greater or wider than the native valveannulus, such as the mitral valve annulus (MVA). In embodiments hereof,such a configuration can reduce the likelihood of migration of valveprosthesis 1400, for example into the ventricle. In embodiments hereof,such a configuration may improve sealing of valve prosthesis 1400against the heart, such as the atrial wall (AW). In some embodimentshereof, frame 1410 is designed to provide axial fixation by creatingtension in the chordae tendinae (CT), which can hold inlet portion 1402of frame 1410 against a native valve annulus (MVA). A transition orsealing zone between an inflow portion and an outflow portion of frame1410 can provide sealing with the patient's anatomy to preventparavalvular leakage of frame 1410. In embodiments hereof, frame 1410 isshaped and sized so as to anchor frame 1410 within a valve annulus byitself or in combination with the chordae tendinae (CT).

FIG. 15 is a cross-sectional view of a frame 1510 in accordance with anembodiment hereof. Frame 1510 can include a central or valve-retainingtubular portion 1504 attached to an inlet portion 1502. In embodimentshereof, inlet portion 1502 may be substantially S-shaped, or may bedescribed as having an S-shaped radial profile. For example, inletportion 1502 can include one or more curves as it radially extends fromproximal or inflow end 1503 of central portion 1504, such as curves1547, 1549, and 1551, which together can approximate an S-shape. Forexample, in some embodiments, inlet portion 1502 includes extension orstrut 1512 that protrudes in a radially outward direction from centralportion 1504 of frame 1510. The substantial “S” shape of inlet portion1502 can be formed by strut 1512 bending in a first curve 1547 frominflow end 1503 towards outflow end 1505, and then bending in a secondcurve 1549 back towards inflow end 1503. In one embodiment of such anS-shape is shown for example in FIG. 15. In embodiments hereof,extension or strut 1512 can additionally bend in a third curve 1551towards a radially inward direction as shown in FIG. 15. Curve 1551 canprevent damage to the atrial tissue by directing the inflow crownsradially inward and away from atrial tissue. Additionally, the inflowcrowns may be rounded or wrapped by an appropriate graft material tominimize damage of the atrial wall.

In one embodiment, frame 1510 may include an outer diameter DA in therange of about 60.37 mm, a valve diameter Dv in the range of about 30.42mm, a valve height Hv between an outflow end 1505 of frame 1510 andinflow end 1503 of frame 1510 in the range of about 16.97 mm, aneffective valve height HEY between outflow end 1505 of frame 1510 andcurve 1549 in the range of about 10.56 mm, an upper s-shape dimensionD_(US) between curve 1547 and 1549 in the range of about 3.14 mm, and alower s-shape dimension D_(LS) between curve 1549 and the first fullnode of the central or valve-retaining tubular portion 1504 from inflowend 1503 in the range of about 2.51 mm.

In embodiments hereof, inlet portion 1502 can be configured to contact apatient's atrial anatomy at a lower point on frame 1510 compared toconventional frame designs. In some embodiments, such a configurationcan serve to increase chordae tension. In embodiments hereof, the shapeand size of inlet portion 1502 can be configured to conform to the shapeof the native mitral annulus and left atrium. In embodiments hereof,such a configuration can result in varying degrees of deformation, fore.g., a flattening, of inlet portion 1502, which can serve to create anexcellent seal between inlet portion 1502 and the native anatomy. Insome embodiments, one or more of the above configurations can serve toreduce paravalvular leakage compared to other frame designs. Inletportion 1502 can be configured to maintain contact throughout apatient's cardiac cycle. In embodiments hereof, changes in chordaetension may be accommodated by partially flattening inlet portion 1502.In embodiments hereof, the flattening of inlet portion 1502 can hold aspring load. In embodiments hereof as changes in the chordae tensionoccur throughout the cardiac cycle, the spring load may serve tomaintain contact and sealing of inlet portion 1502 against the tissuedespite the changing tension.

FIGS. 16, 16A and 16B illustrate a frame 1610 in accordance with anotherembodiment hereof. FIG. 16 illustrates a front or side view of frame1610. FIG. 16A illustrates a view of frame 1610 implanted in a nativemitral valve site (MV) and FIG. 16B illustrates an enlarged view of aportion of FIG. 16A. Valve site (MV) includes an annulus (MVA), nativeleaflets (AL, PL), chordae tendinae (CT), and papillary muscles (PM).Frame 1610 may include support arms 1606A, 1606B, inflow portion 1602,and a central or valve-retaining tubular portion 1604. A partiallyhourglass-shape of frame 1610 along central portion 1604 includes areduced-waist region 1625 and may be configured to capture or pinch amuscular ridge of annulus (MVA) to provide axial fixation of frame 1610within valve site (MV). The hourglass shape portion of frame 1610 may beformed by the atrial portion of the frame, i.e., inflow portion 1602,and the ventricular portion of the frame, i.e., outflow portions 1605that outwardly extend from the reduced-waist region 1625, such thatframe 1610 axially engages, fixates, or pinches the annulus from boththe atrial and ventricular sides of the annulus. An example of such aconfiguration is shown in FIGS. 16, 16A and 16B. Other suitableconfigurations may be used. In embodiments hereof, theoutwardly-extending outflow portions 1605 along central portion 1604 arepositioned along a circumference of the central portion 1604 about 90degrees from each support arm 1606A, 1606B, or stated another way ispositioned along the circumference of central portion 1604 approximatelyhalf way between the support arms 1606A, 1606B. In another embodiment,outwardly-extending outflow portions 1605 and inflow portion 1602 thatform the hourglass shape portion of frame 1610 may specifically targetthe annulus and/or commissures of the native valve. Frame 1610 may alsoprovide axial fixation by creating tensioning of the chordae tendinae(CT). In some embodiments, the valve prosthesis may comprise one or mores-shaped portions or components. In some embodiments, the valveprosthesis may comprise an s-shaped inflow portion 1602. The s-shapeinflow portion may comprise various dimensions relative to the centralor valve-retaining tubular portion of the frame as previously described.In some embodiments, the valve prosthesis may comprise s-shaped outflowportions 1605. The s-shape outflow portions may comprise variousdimensions relative to the central or valve-retaining tubular portion ofthe frame as previously described. In some embodiments, one or moresupport arms 1606A, 1606B may comprise an s-shaped portion.

FIG. 17 is a front or side view of a valve prosthesis 1700 in accordancewith an embodiment hereof. FIG. 17A is a top or inflow view of valveprosthesis 1700 of FIG. 17 taken in the direction of line A-A therein.Valve prosthesis 1700 includes a valve body or component 1720 supportedwithin a frame or support structure 1710. Frame 1710 includes an inletportion 1702, an hourglass-shaped central or valve-retaining tubularportion 1704 and support arms 1706. Support arms 1706 may be configuredto capture leaflets during delivery of valve prosthesis 1700. Centralportion 1704 may be configured to pinch a muscular ridge of the nativeannulus when implanted therein. The reduced-waist region of thehourglass shape or profile of frame 1710 may be located on or definedwithin central portion 1704 around the entire circumference of frame1710, such as the configuration is shown in FIGS. 17 and 17A. Frame 1710may also provide axial fixation by creating tensioning of the chordaetendinae (CT).

FIG. 18 is a front or side view of a frame 1810 for a valve prosthesis1800 in accordance with an embodiment hereof. FIG. 18A is a top orinflow view of valve prosthesis 1800 utilizing the frame 1810 of FIG. 18taken in the direction of line A-A therein. FIG. 18B shows valveprosthesis 1800 implanted in a native valve site (MV) with FIG. 18Cbeing an enlarged view of a portion of FIG. 18B. The valve site (MV)depicted in FIGS. 18B and 18C includes annulus (MVA), chordae tendinae(CT), and papillary muscles (PM).

Valve prosthesis 1800 includes a valve body or component 1820 supportedby frame 1810. Frame 1810 may include an inlet portion 1802, anhourglass-shape along a central or valve-retaining tubular portion 1804and support arms 1806. Support arms 1806 may be configured to capturethe native valve leaflets during device delivery. Axial fixation offrame 1810 can be achieved through the hourglass-shape of frame 1810along central portion 1804 that pinches a muscular ridge of the nativeannulus (MVA). The hourglass shape portion of frame 1810 may be formedby the atrial portion of the frame, i.e., inflow portion 1802, and aventricular portion of the frame, i.e., second arms 1871A, 1871B thatoutwardly extend from the reduced-waist region 1825, such that frame1810 axially engages, fixates, or pinches the annulus from both theatrial and ventricular sides of the annulus. In embodiments hereof, theoutwardly-extending second arms 1871A, 1871B along central portion 1804extend from each support arm 1806 to be disposed along a circumferenceof the central portion about 90 degrees from each support arm, or statedanother way to be formed along the circumference of central portion 1804approximately half way between the support arms 1806. In the embodimentof FIG. 18, the atrial and ventricular portions of frame 1810 that formthe hourglass shape originate from the same node location of centralportion 1804. In another embodiment shown in FIG. 18D, support arms1806D and corresponding second arms 1871D of frame 1810D may originatefrom a different node location of central portion 1804D than inflowportion 1802D such that a gap G is present therebetween withinreduced-waist region 1825D. In another embodiment shown in FIG. 18E,support arms 1806E and second arms 1871E of frame 1810E are separatestructures that act independently from one and other. As in theembodiment of FIG. 18, inflow portion 1802E of frame 1810E and secondarms 1871E of frame 1810E may originate from the same node location ofcentral portion 1804D. In another embodiment, inflow portion 1802E offrame 1810E and second arms 1871E of frame 1810E may originate fromdifferent node locations of central portion 1804E similar to theembodiment of FIG. 18D.

In some embodiments, frame 1810 may geometrically vary along its length.For example, frame 1810 may comprise a geometric cross-sectional shapethat matches the shape of a native valve annulus. Frame 1810 may have aportion with an elliptical cross-section such as an outflow or distalend portion 1805 and/or frame 1810 may have a portion having a tubularor D-shaped cross-section, for example, to match the shape of the nativevalve annulus. The larger diameter of the ellipse or D-shape frameportion may be positioned near the mitral valve commissures of thenative valve (MV). The shorter diameter of the ellipse or D-shape frameportion may be positioned near the aorta-mitral fibrous continuity ofthe native valve. Although outflow end 1805 may be elliptical, valvebody 1820 attached to frame 1810 may remain cylindrical or circular. Oneexample of such a configuration is shown in FIGS. 18, 18A, 18B and 18C.Frame 1810 may also provide axial fixation by creating by creatingtensioning of the chordae tendinae (CT). Support arms 1806 may transfertension to the chordae tendinae (CT) and/or the support arms 1806 mayapply a force, for example at the distal ends of the support arms, tothe ventricular side of the annulus to prevent movement or migration ofthe prosthesis into the atrium. In some embodiments, valve prosthesismay comprise one or more support arms 1806. In some embodiments, valveprosthesis may comprise one or more support arms for engaging orcapturing valve leaflets and one or more support arms for engaging oneor more commissures. For example, in one embodiment, valve prosthesisincludes one support arm positioned or located in the middle of theposterior leaflet of a native mitral valve and two support armspositioned or located at the left and right trigone, commissures, orwith reference to FIG. 1A, the A1 and A3 locations of the anteriorleaflet. For example, in one embodiment, the valve prosthesis includesone support arm positioned or located in the middle of the anteriorleaflet and two support arms positioned or located, with reference toFIG. 1A, at the P1 and P3 portions of the posterior leaflet. In someembodiments, support arms may engage or interact with leaflets as wellas commissures. In some embodiments, support arms may apply one or moreforces such as a radial force, a axial force, a lateral force, an inwardforce, an outward force, an upstream force, and/or a downstream force toone or more heart structures and/or tissues.

FIGS. 19 and 19A illustrate a valve prosthesis 1900 having a prostheticvalve component with four valve leaflets 1924. FIG. 19 is an outflow orbottom front perspective view of valve prosthesis 1900 in an openposition in accordance with an embodiment hereof. FIG. 19A illustratesan outflow or bottom front perspective view of valve prosthesis 1900 ofFIG. 19 in a closed position. Valve prosthesis 1900 includes a frame1910 along with a valve body or component including four prostheticvalve leaflets 1924. An outflow end 1905 of frame 1910 may flareoutwardly to allow for gaps G1-G4 between an outflow end 1950 of eachvalve leaflet 1924 and outflow end 1905 of frame 1910. In accordancewith embodiments hereof, frame 1910 may be adapted to include one ormore support arms as described herein.

FIGS. 20 and 20A illustrate a valve prosthesis 2000. FIG. 20 illustratesan outflow or bottom front perspective view of valve prosthesis 2000 inan open position. FIG. 20A illustrates an outflow or bottom view ofvalve prosthesis 2000 taken in the direction of line A-A in FIG. 20.Valve prosthesis 2000 may include a frame 2010 with a valve body orcomponent including prosthetic valve leaflets 2024A, 2024B, 2024Csecured therein. As shown, for example in FIG. 20A, a transversecross-section of a valve outlet 2052 of frame 2010 may be a roundedtriangle with each vertex 2052A, 2052B, 2052C of the triangle alignedwith a corresponding leaflet 2024A, 2024B, 2024C of the valve body toprovide gaps G_(A), G_(B), G_(C) between an outflow end 2005 of frame2010 and the outflow end 2050 of valve leaflets 2024A, 2024B, 2024C whenthe leaflets are fully open. In embodiments hereof, a mid-section ormidpoint of sides 2052D, 2052E, 2052F of the rounded triangle defined byvalve outlet 2052 of frame 2010 are aligned with correspondingcommissures 2024D, 2024E, 2024F of the valve body. A transversecross-section of a valve base 2054 of frame 2010 can be a roundedtriangular and rotated about 60 degrees relative to the transversecross-section of valve outlet 2052 of frame 2010 so that the valve bodyforms a roughly cylindrical shape, as shown in FIGS. 20 and 20A. Inaccordance with embodiments hereof, frame 2010 may be adapted to includeone or more support arms as described herein.

FIGS. 21 and 21A illustrate a valve prosthesis 2100. FIG. 21 illustratesvalve prosthesis 2100 in an open position with FIG. 21A depicting anoutflow or bottom view of valve prosthesis 2100 in the open position.Valve prosthesis 2100 includes a frame 2110 having a valve body orcomponent including prosthetic valve leaflets 2124A, 2124B, 2124Csecured therein. In accordance with embodiments hereof, frame 2110 maybe adapted to include one or more support arms as described herein.Frame 2110 is configured to allow for gaps G_(A), G_(B), G_(C) betweenan outflow end 2150 of valve leaflets 2124A, 2124B, 2124C and an outflowend 2105 of frame 2110 when valve leaflets 2124A, 2124B, 2124C are fullyopen. In embodiments hereof, gaps G_(A), G_(B), G_(C) can be sized andshaped to minimize or eliminate contact between valve leaflets 2124A,2124B, 2124C and frame 2110. In embodiments hereof, gaps G_(A), G_(B),G_(C) can be up to 5 millimeters wide. In other embodiments hereof, gapsG_(A), G_(B), G_(C) can be larger than 5 millimeters.

Valve outlet 2152 of frame 2110 includes three sides 2152D, 2152E, 2152Fthat curve inward from apexes or vertex 2052A, 2052B, 2052C. Inembodiments hereof, a mid-section or midpoint of sides 2152D, 2152E,2152F are aligned with corresponding commissures 2124D, 2124E, 2124F ofthe valve body. The overall shape of the transverse cross-section ofvalve outlet 2152 can be described as clover-leaf shaped. In addition,sides of the rounded triangle of valve base 2154 curve inward and canalso be described as clover-leaf shaped. The cross-section of valve base2154 can be rotated about 60 degrees relative to the cross-section ofvalve outlet 2152 so that the valve forms a roughly cylindrical shape.In embodiments hereof, valve base 2154 can be substantially cylindricaland valve outlet 2152 can flare out from valve base 2154. In embodimentshereof, valve leaflets 2124A, 2124B, 2124C can be attached at valve base2154.

FIG. 22A depicts a patterned tube 2210A for forming a frame 2210B inaccordance with an embodiment hereof that has been laid flat forillustrative purposes. FIG. 22B depicts a saddle shape of frame 2210Bwhen expanded. In some embodiments, a non-planar or saddle shape of oneor more of the various frames or portions thereof as described hereincan be achieved by changing the location of nodes formed within theframe. In some embodiments, a non-planar or saddle shape of one or moreof the various frames or portions thereof as described herein can beachieved through a shape setting process. In some embodiments, acombination of shape setting and node placement patterns may be used toform non-planar or saddle shapes of one or more of the various frames orportions thereof as described herein. For example, a laser cut patternof a frame can be modified, along with new fixtures for shape setting toachieve a non-planar configuration. In particular, patterned tube 2210Aincludes nodes 2260 arranged in a sinusoidal pattern. In someembodiments, such a configuration can have the effect of changing theshape of frame 2210B when frame 2210B is expanded. The sinusoidalpattern of nodes 2260 within patterned tube 2210A can, for example,result in a three dimensional saddle shape 2262 of frame 2210B, shownfor example in FIG. 22B, that can mimic the native anatomy at a valveannulus, such as a mitral valve. In some embodiments, patterned tube2210A can include a saddle-shaped inflow section 2202A and an unmodifiedcenter or valve-retaining tubular section 2204A, such as inflow portion202 of valve prosthesis 200 shown in FIG. 2. In some embodiments, ashape-setting process alone may be used without a sinusoidal pattern ofnodes to create a frame having an s-shaped and/or saddle shaped inflowsection that matches the saddle shape of a native valve annulus.

FIGS. 23 and 23A illustrate a frame 2310 for a valve prosthesis inaccordance with another embodiment hereof. FIG. 23 is a front or sideview of frame 2310 with FIG. 23A being an inflow or top view of frame2310 taken in the direction of line A-A in FIG. 23. Frame 2310 mayinclude central or valve-retaining tubular portion 2304, inlet or inflowportion 2302, and chordae engagement or guiding element 2370. A chordaeguiding element 2370 may extend from each support arm 2306 and may beconfigured to engage chordae of the native valve site. As describedabove, chordae tendinae connect to native valve leaflets and act like“tie rods” in an engineering sense. As described above in someembodiments hereof, it may be desirable to impart tension onto thechordae tendinae with the support arms, such as support arms 2306.However, excessive tension can cause the chordae tendinae to rupturewhich can reduce the effectiveness of a valve prosthesis. In order toaddress such a concern in embodiments hereof a shape and location of thesupport arms, such as the shape and location of support arms 2306 onframe 2310 of FIGS. 23 and 23A, can reduce tension imparted onto thechordae tendinae by the support arms.

In embodiments hereof, chordae engagement or guiding element 2370 can beformed by a rigid wire material and can be shaped to avoid hard anglesand/or sharp edges. In embodiments hereof, chordae guiding element 2370may be the same thickness and material as the support arms 2306. Inembodiments hereof, chordae guiding element 2370 may be bent in theshape of a semi-circle, oval, lobe, or other suitable shape. Inembodiments hereof, one or more chordae engagement or guiding elementsmay be connected, coupled, attached, and/or extend from one or morelocations on one or more support arms, the outflow portion, the inflowportion, and/or the central portion of the valve prosthesis. Inembodiments hereof, one or more support arms, the inflow portion, thecentral portion, and/or the outflow portion of the valve prosthesis maycomprise one or more chordae engagement or guiding elements. One or morechordae engagement elements 2370 of frame 2310 may be configured toangle the chordae tendinae so that the chordae are stretched to restrictmovement of a valve prosthesis in an upstream direction of blood flow atthe valve site. In embodiments hereof, chordae guiding element 2370 maybe configured to interact with one or more native valve leaflets insteadof the chordae tendinae. In embodiments hereof, one or more of the aboveconfigurations can be used in combination with other coatings,coverings, or configurations to reduce chordae abrasion or rupture, asdescribed in more detail below. In embodiments hereof, any corners ofone or both of support arms 2306 and chordae guiding elements 2370 maybe rounded, which in some embodiments can avoid sharp corners that cancause chordae abrasion or rupture. In embodiments hereof, chordaeguiding element 2370 is positioned such that the chordae tendinae arestretched to prevent movement of the valve prosthesis relative to thenative valve over the course of the cardiac cycle, without rupturing thechordae tendinae. In embodiments hereof, such a configuration canprovide added stability to the valve prosthesis while preventing damageto the chordae. In some embodiments, chordae guiding element 2370 may bedirectly attached to support arm 2306 and may extend outward from theleaflet securing arm. A first end and a second end of chordae guidingelement 2370 may be attached to central portion 2304 of frame 2310. Inembodiments hereof, one end of chordae guiding elements 2370 may bedirectly attached to support arm 2306 and a second end of chordaeguiding element 2370 may be directly attached to central portion 2304.In some embodiments, chordae guiding element 2370 and/or support arms2306 may contain one or more features for holding or restricting motionof the leaflets or chordae. These features may include, but are notlimited to, barbs for engaging the leaflets and/or chordae. In someembodiments, leaflets and/or chordae, and/or portions thereof, may beclamped, pinched, or otherwise engaged or fixed by or between thesupport arms 2306 and/or the chordae guiding elements 2370.

In embodiments hereof, chordae guiding element 2370 may reduce bendingof the native chordae by redistributing the force applied by support arm2306 to the chordae. In embodiments hereof, an outflow end 2364 ofsupport arm 2306 is longitudinally offset from an outflow end 2366 ofchordae guiding element 2370 by a distance to reduce the bending of thechordae. The longitudinal offset can be, for example, from about 1 mm toabout 5 mm in the longitudinal direction. In embodiments hereof, outflowend 2364 of support arm 2306 is laterally offset from outflow end 2366of chordae guiding element 2370 by a distance to reduce the bending ofthe chordae. The lateral offset can be, for example, from about 1 mm toabout 5 mm in the lateral direction.

In embodiments hereof, chordae guiding element 2370 may be configured tocreate a tapered entry for the chordae. In embodiments hereof, alongitudinal and/or lateral offset between support arms 2306 and chordaeguiding element 2370 may be configured to guide chordae substantiallyalong a portion of an arc, such as along a portion of parabolic arc PA(shown in broken lines) in FIG. 23. In embodiments hereof, arc PA can becircular rather than parabolic, stepped, or another desired shape. Inembodiments hereof, arc PA can guide chordae exiting support arm 2306and chordae guiding element 2370 to approximate a native anatomicalangle. In embodiments hereof, such a configuration can reduce abrasionof the chordae and/or maintain a desired chordal tension. In embodimentshereof, a desired chordal tension is sufficient to prevent frame 2310from lifting into the atrium. In embodiments hereof, a desired chordaltension is sufficient to substantially prevent frame 2310 from movingand/or rocking during the cardiac cycle. In embodiments hereof, theangle formed by arc PA can serve to decrease an angle of entry of thechordae into support arm 2306, which can reduce chordal abrasion forcesacting on the chordae from frame 2310. In embodiments hereof, supportarms 2306 and chordae guiding element 2370 are configured tosubstantially eliminate bending of the chordae. In some embodiments,support arms 2306 and chordae guiding element 2370 are configured tobend the chordae less than approximately 90 degrees. In embodimentshereof, chordae are guided solely by chordae guiding element 2370 andare guided by chordae guiding element so as not to touch support arms2306.

FIG. 24 illustrates a simplified drawing of a support arm 2406. Supportarm 2406 may include a first end 2473 and a second end 2475. One or bothof first end 2473 and second end 2475 may be connected to the same ordifferent portions of the frame (not shown). Support arm 2406 mayinclude a first and second chordae guiding element 2470A, 2470B, whichcan function similarly to the chordae guiding elements described above.Each chordae guiding element 2470A, 2470B may include a first end 2476attached to support arm 2406 and a second end 2478 attached to theframe. In embodiments hereof, first end 2476 may also be connected tothe frame. In some embodiments hereof, both first end 2476 and secondend 2478 of each chordae guiding element 2470A, 2470B may be connectedto support arm 2406. In some embodiments hereof, both ends 2476 ofelements 2470B may be connected to each other instead of or in additionto connecting to support arm 2406.

With reference to FIGS. 5A-5D the operation of support arms inaccordance with some embodiments hereof will be described. Frame 310 isutilized in a valve prosthesis 300 with a valve component 320 attachedwithin the interior portion thereof, and has two support arms orpositioning elements 306A, 306B, although more than two and less thantwo support arms or positioning elements may alternatively be used inembodiments hereof. Valve component 320 is a prosthetic bicuspid valvehaving two leaflets 324A, 324B, although other configurations, such as atricuspid leaflet configuration, may alternatively be used inembodiments hereof. Each support arm 306A, 306B may bend or rotate morethan ninety degrees with respect to its compressed, deliveryconfiguration during deployment of valve prosthesis 300. In oneembodiment, each support arm 306A, 306B rotates between 135 degrees and180 degrees during deployment of valve prosthesis 300. In a deliveryconfiguration of FIGS. 5A and 5C, each support arm 306A, 306B maydistally extend from distal or outflow end 305 of frame 310. Whenreleased from a delivery sheath or other delivery device (not shown),each support arm 306A, 306B may gradually bend outwardly and thentowards an outer surface of the delivery device or frame 310 until itreaches a deployed configuration of FIGS. 5B and 5D in which eachsupport arm 306A, 306B proximally extends from distal or outflow end 305of frame 310. Once deployed, support arms 306A, 306B may function toposition and anchor valve prosthesis 300 at a native valve target site,such as a mitral valve target site. In one embodiment, when deployed ata native mitral valve target site, the configuration/structure of avalve prosthesis as well as the delivery system and method of use mustaccommodate the size of the left ventricle and refrain from obstructingthe left ventricular outflow tract. By rotating from an initialdistally-extending configuration to a final proximally-extendingconfiguration, support arm 306A, 306B as well as those shown anddescribed in other embodiments hereof are particularly configured to bedeployed within a native mitral valve target site as will be explainedin more detail below.

As discussed above, each positioning element or support arm may becoupled to a distal or outflow end portion of the frame of the valveprosthesis. In embodiments hereof, each support arm may be coupled tothe frame at multiple connection points. More specifically referring toFIG. 5A and FIG. 25 that is an enlarged portion of FIG. 5A, each supportarm 306A, 306B may be coupled to distal end 305 of frame 310 via twoV-shaped connectors 390A, 390AA and 390B, 390BB, respectively, such thatfour connection points A1, A2, A3, A4 and B1, B2, B3, B4, respectively,are located between each support arm 306A, 306B and frame 310. In oneembodiment, the eight connection points A1, A2, A3, A4, B1, B2, B3, B4are approximately equally spaced around the perimeter of distal end 305of frame 310 and collectively function to prevent the prosthetic valveleaflets from obstructing the outflow end of valve prosthesis 300 andthe left ventricular outflow tract. Stated another way, V-shapedconnectors 390A, 390AA, 390B, 390BB increase the number of connectionpoints between each support arm 306A, 306B, respectively, and frame 310,and thereby shorten or minimize the open space or distance betweenadjacent connection points. V-shaped connectors 390A, 390AA, 390B, 390BBmay act as an obstacle in the path that the prosthetic valve leafletswould follow when overlapping onto frame 310 and can thereby keep theflow path clear. Although described as “V-shaped connectors,” it will beapparent to those of ordinary skill in the art that two straightcomponents formed generally in the shape of a “V” may be utilized inembodiments hereof rather than one single V-shaped component. Inaddition, although described with respect to support arms 306A, 306B andframe 310, such connectors may be utilized for forming multipleconnection points between any embodiment described herein. In someembodiments, a graft material may be used between connection points B1and B4 to help create a clear flow path as described above.

In embodiments hereof and as described herein, support arms 306A, 306Band frame 310 may be formed as an integral unitary structure, such as bylaser cutting or etching the support arms and frame from a single hollowtube or sheet. In another embodiment, V-shaped connectors 390A, 390AA,390B, 390BB and/or support arms 306A, 306B may be separate componentsthat are formed separately and mechanically coupled to each other and toframe 310 via any suitable mechanical method, including welding,soldering, or by another mechanical method.

In order to lower the amount of stress and/or strain that occurs inV-shaped connectors 390A, 390AA, 390B, 390BB as support arms 306A, 306Btransform between the initial distally-extending compressedconfiguration and the final proximally-extending deployed configuration,the width of the wire(s) or tubular member(s) which form V-shapedconnectors 390A, 390AA, 390B, 390BB may be increased as compared to thewidth or dimension of support arms 306A, 306B as well as compared to thewidth or dimension of the wire or tubular member which forms frame 310.More particularly, FIG. 25A illustrates a sectional view along line A-Aof FIG. 25 showing a strut 323 of V-shaped connector 390B according toan embodiment hereof. A reference width W_(R) is shown in phantom inFIG. 25A and represents the width of the wire or tubular member whichforms frame 310 and/or support arms 306A, 306B. A width W_(S) of strut323B is widened or increased relative to width W_(R), thereby increasingthe amount of material of V-shaped connector 390B such that it canhandle the deformation that occurs thereto during deployment of valveprosthesis 300. In order to widen or increase the width of strut 323,material may be added or banded to strut 323 around the width directionthereof. In an embodiment, material may be added to include the width ofstrut 323 up to three times of width W_(R). Preferably, a thicknessT_(S) of strut 323 is not increased relative to the thickness of thewire or tubular member which forms frame 310 due to size constraints onthe compressed outer diameter or profile of valve prosthesis 300 when ina compressed configuration. As utilized herein, thickness T_(S) of strut323 refers to the strut material that extends in a radial directionrelative to frame 310. Although illustrated as constant or uniform,thickness T_(S) of strut 323 may vary or increase from an inner surfacerelative to an outer surface of strut 323.

FIGS. 26A-26F illustrates various configurations of generally U-shapedor V-shaped support arms according to embodiments hereof. Referring alsoto FIG. 26A, support arm 2606A is generally shown as being a wire ortubular structure formed into a U-shaped or generally U-shapedconfiguration such that the support arm has two straight side segments2680A, 2682A with a bottom curved segment 2684A. As will be understoodby those of ordinary skill in the art, “side” and “bottom” are relativeterms and utilized herein for illustration purposes only. The straightside segments may be parallel to each other as shown in FIG. 26A, or maybe slanted or angled away from each other as shown in support arm 2606Bof FIG. 26B in which two straight slanted side segments 2680B, 2682Bflare apart as they extend from bottom curved segment 2684B. As utilizedherein, “generally” U-shaped includes wire or tubular structures formedinto: a horseshoe shape support arm 2606C as shown in FIG. 26C in whichtwo curved side segments 2680C, 2682C have ends that converge togetheras they extend from bottom curved segment 2684C; a semi-circle supportarm 2606D as shown in FIG. 26D; and an oblong shape support arm 2606F asshown in FIG. 26F in which two parallel straight side segments 2680F,2682F have a straight bottom segment 2684F therebetween. In anotherembodiment hereof, the positioning elements may be generally V-shaped asshown in support arm 2606E of FIG. 26E in which two straight slantedside segments 2680C, 2682C are connected together by a curved apex2684E. In some embodiments, one or more support arms, as describedherein, may be considerably longer, shorter, wider, or narrower thanshown. In some embodiments, one or more support arms, as describedherein, may be narrower at the base, bottom or proximal end portionwhere the support arms couple to the inflow portion, central portionand/or the outflow portion of the valve prosthesis and wider at the topor distal end portion of the support arm. In some embodiments, one ormore support arms, as described herein, may be wider at the base,bottom, or proximal end portion where the support arms couple to theinflow portion, central portion and/or the outflow portion of the valveprosthesis and narrower at the top or distal end portion of the supportarm. In some embodiments, one or more support arms, as described herein,may be configured to be a shape and size that can provide a positioningfunction, valve leaflet capturing function, a stabilization function, ananti-migration function, and/or an anchoring function for valveprosthesis in accordance herewith when the prosthesis is deployed at anative valve site. In some embodiments, one or more support arms, asdescribed herein, may interact, engage, capture, clamp, push against oneor more native tissues or structures such as valve leaflets, chordae,annulus, ventricle, and/or atrium. In some embodiments, one or moresupport arms, as described herein, may comprise a first portion thatextends in a forward direction and a second portion that extends in abackward direction. In some embodiments, one or more support arms, asdescribed herein, may comprise a first portion that extends in abackward direction and a second portion that extends in a forwarddirection. In some embodiments, one or more support arms, as describedherein, may be connected, coupled, attached, and/or extend from one ormore locations positioned on the inflow portion, the central portionand/or the outflow portion of the valve prosthesis. For example, if thevalve prosthesis is positioned within the native mitral valve annulus,the support arms may extend from the frame of valve prosthesis inaccordance herewith on the ventricular or outflow side of the mitralvalve and provide interference with the native valve leaflets and/or thewalls of the left ventricle, thereby inhibiting motion of the valveprosthesis.

FIGS. 27A, 27B, 27C, 27D illustrate an embodiment of a valve prosthesis2700 having support arms 2706A, 2706B with double or dual support armsthat may be utilized in any embodiment described herein. FIGS. 27A and27C are schematic side and top views, respectively, of valve prosthesis2700 having support arms 2706A, 2706B with outer and inner U-shapedsupport arms according to an embodiment hereof, wherein valve prosthesis2700 is in a delivery or compressed configuration with the support arms2706A, 2706B distally extending from a distal end 2705 of theprosthesis. FIGS. 27B and 27D are schematic side and top views,respectively, of valve prosthesis 2700 of FIGS. 27A and 27C, wherein thevalve prosthesis is in an expanded or deployed configuration withsupport arms 2706A, 2706B proximally extending from distal end 2705 ofthe prosthesis. More particularly, FIGS. 27C and 27D are a side view ofthe frame 2710 as shown in FIGS. 27A and 27B rotated 90° about alongitudinal axis L_(A) thereof from the orientation shown in FIGS. 27Aand 27B.

Similar to embodiments described above, valve prosthesis 2700 mayinclude a frame, framework or stent 2710, a valve component 2720attached within the interior portion of frame 2710 that is capable ofblocking flow in one direction to regulate flow through valve prosthesis2700 via leaflets 2724A, 2724B, and two support arms 2706A, 2706B. Frame2710 of valve prosthesis 2700 may be a generally tubular expandable bodyhaving a stepped outer diameter or profile extending between a proximalend 2703 and distal end 2705. Similar to embodiments described above,the stepped outer diameter of frame 2710 may include a distal, outflow,central or ventricular segment 2704 and a proximal, inflow or atrialsegment 2702 having an expanded diameter which is greater than theexpanded diameter of outflow segment 2704.

Support arms 2706A, 2706B may extend from opposing sides of frame 2710.With reference to support arm 2706A in FIG. 27A, support arm 2706A mayinclude a first or outer U-shaped support arm 2786A and a second orinner U-shaped support arm 2788A that each distally extend from a distalend 2705 of frame 2710. Although not shown in the figures, support arm2706B may also include a second or inner U-shaped support arm within anouter U-shaped support arm. When released from a delivery sheath (notshown), each of the U-shaped support arms may gradually bend outwardlyand then towards an outer surface of the delivery device or frame of thevalve prosthesis until they transform from their compressedconfiguration of FIGS. 27A and 27C to their deployed configuration ofFIGS. 27B and 27D in which each of the U-shaped support arms proximallyextends from distal end 2705 of frame 2710. As in embodiments describedabove, each of the U-shaped support arms may bend or rotate more thanninety degrees with respect to a compressed, delivery configurationduring deployment of valve prosthesis 2700. In one embodiment, eachU-shaped support arm rotates between 135 degrees and 180 degrees duringdeployment of valve prosthesis 2700. Compared to a single U-shapedsupport arm, outer and inner U-shaped support arms may provideadditional spring force for improved anchoring and/or positioning of thevalve prosthesis.

Adjacent outer and inner U-shaped support arms of each support arm2706A, 2706B may be coupled together. With reference to support arm2706A in FIG. 27A, adjacent outer and inner U-shaped support arms 2786A,2788A of support arm 2706A may be coupled together via a connector 2787Awhich ensures that both U-shaped support arms of support arm 2706Aremain in the same plane during deployment. Connector 2787A may have aflared V-shaped configuration in which an apex 2745 of connector 2787Ais coupled to a peak or crest 2743 of inner support arm 2788A. Moreparticularly, connector 2787A may include two curved legs 2746A, 2746B.First ends of legs 2746A, 2746B may be coupled to peak 2743 of innersupport arm 2788A, and curved legs 2746A, 2746B of connector 2787A mayextend or flare away from each other such that second ends of legs2746A, 2746B may be coupled adjacent to or on opposing sides of a peakor crest 2741 of outer support arm 2786A. Due to the curved legs 2746A,2746B of connector 2787A, the distance or space between the crowns ofouter and inner U-shaped support arms may be adjustable and allowed tochange. Legs 2746A, 2746B may allow distance or space between peak 2743of inner support arm 2788A and peak 2741 of outer support arm 2786Abecause the curved legs of connector 2787A may bend, resulting in ashorter distance between peak 2743 and peak 2141, or the legs ofconnector 2787A may straighten, resulting in a greater distance betweenpeak 2743 and peak 2141. In some embodiments, one or more support armsmay include outer and inner support arm members coupled togetherdirectly without the use of a connector, for example as shown in FIG. 6.In some embodiments, one or more support arms may include outer andinner support arm members not coupled together, for example as shown inFIG. 17. In some embodiments, one or more support arms may include twoor more support arm members coupled together with or without the use ofa connector, for example as shown in FIG. 22. In some embodiments, oneor more support arms may include two or more support arm members notcoupled together and/or two or more support arm members coupled togetherwith or without the use of a connector, for example as shown in FIGS.30B and 42B.

The distance or space between peak 2743 and peak 2741 may increaseduring crimping when valve prosthesis 2700 is in a compressedconfiguration shown in FIG. 27A, 27C, and the distance or space maydecrease during expansion when valve prosthesis 2700 is in a deployedconfiguration. Connector 2787A, as well as the inner and outer U-shapedsupport arms, may be laser cut from a tube of self-expanding materialand thereby integrally formed as part of the frame 2710 of the valveprosthesis, or may be formed separately and subsequently attached to theframe 2710. Although connector 2787A is only visible in FIGS. 27A, 27Bbetween inner support arm 2788A and outer support arm 2786A, it will beunderstood by one of ordinary skill in the art that such a connector maycouple the outer and inner support arms of support arm 2706B that alsoextend from distal end 2705 of valve prosthesis 2700.

FIGS. 28A, 28B, 28C illustrate an embodiment of a valve prosthesis 2800including a lattice frame or stent framework 2810 and positioningelements or support arms 2806A, 2806B with dual U-shaped support armsthat distally extend from a distal end 2805 of the valve prosthesis.More particularly, support arms 2806A, 2806B may include a first orouter U-shaped support arm 2886A, 2886B, respectfully, and a second orinner U-shaped support arm 2888A, 2888B that may each bend or rotatemore than ninety degrees with respect to a compressed, deliveryconfiguration during deployment. Each outer support arm may be connectedto a respective inner support arm via a connector, such as connector2887A shown in FIGS. 28A and 28C, and as described above with respect toconnector 2787A. In the embodiment of FIGS. 28A, 28B, 28C, the U-shapedsupport arms may extend from the distalmost crowns or apexes 2817 oflattice frame 2810. Compared to the embodiment shown in FIGS. 29A-29C,frame 2810 and thus valve prosthesis 2800 may have a smaller crimpedprofile for delivery.

FIGS. 29A, 29B, 29C illustrate an embodiment of a valve prosthesis 2900that is similar to valve prosthesis 2800, except that support arms2906A, 2906B do not extend from distalmost crowns or apexes 2917 of alattice frame 2910. Rather, support arms 2906A, 2906B may extend frombetween the distalmost crowns or apexes 2917 of a lattice frame 2910. Asbest shown in FIG. 29B, in order to shorten or minimize the open spaceor distance D between adjacent support arms 2906A, 2906B, support arms2906A, 2906B may extend from opposing sides of a distalmost crown 2917such that the support arms are separated only by the width of the crown.More particularly, support arms 2906A, 2906B may distally extend from adistal end 2905 of the valve prosthesis and may include a first or outerU-shaped support arm 2986A, 2986B, respectfully, and a second or innerU-shaped support arm 2988A, 2988B, respectively, that may each bend orrotate more than ninety degrees with respect to its compressed, deliveryconfiguration during deployment. Each outer support arm may be connectedto a respective inner support arm via a connector, such as connector2987A shown in FIGS. 29A, 29C and as described above with respect toconnector 2787A. Support arms 2906A, 2906B may extend from between thedistalmost crowns or apexes 2917 of lattice frame 2910 to minimize openspace or distance D and thereby prevent the prosthetic valve leafletsfrom obstructing the outflow end of valve prosthesis 2900 and the leftventricular outflow tract (LVOT). Outer U-shaped support arms of supportarms 2906A, 2906B may be closer together, and act as an obstacle in thepath that the prosthetic valve leaflets would follow when overlappingonto frame 2910 and thereby keep the flow path clear. Another benefit ofextending support arms 2906A, 2906B from between the distalmost crownsor apexes 2917 of lattice frame 2910 is that the support arms may belocated more proximal along the prosthesis compared to the embodimentshown in FIGS. 28A-28C, which minimizes the length or amount of thevalve prosthesis that projects or extends in the left ventricle.

FIGS. 30A and 30 illustrate another embodiment of a valve prosthesis3000 that is similar to valve prosthesis 2900, except that each supportarm or positioning element includes triple support arms for additionalspring force for improved anchoring and/or positioning of the valveprosthesis. Each support arm 3006 may extend from between the distalmostcrowns of a distal end 3005 of a lattice stent or frame 3010 and mayinclude a first or outer U-shaped support arm 3086A, a second orintermediate U-shaped support arm 3088A, and a third or inner U-shapedsupport arm 3092A. When released from a delivery sheath (not shown inFIG. 30A or FIG. 30B), all of the U-shaped support arms may graduallybend outwardly and then towards an outer surface of the delivery deviceor frame of the valve prosthesis until they reach a deployedconfiguration of FIG. 30A and FIG. 30B in which all of the U-shapedsupport arms may proximally extend from distal end 3005 of frame 3010.As in embodiments described above, all of the U-shaped support arms maybend or rotate more than ninety degrees with respect to a compressed,delivery configuration during deployment of valve prosthesis 3000. In anembodiment, each U-shaped support may arm rotate between 135 degrees and180 degrees during deployment of valve prosthesis 3000. Although onlyone support arm or positioning element is shown and described withreference to FIGS. 30A, 30B, it will be understood by those of ordinaryskill in the art that valve prosthesis 3000 may include at least twosupport arms extending from opposing sides of the prosthesis. Eachsupport arm may include triple U-shaped support arms for anchoringand/or positioning the valve prosthesis.

Adjacent support arms of each positioning element may be coupledtogether via a connector which ensures that each support arm of thepositioning element remains in the same plane during deployment. Morespecifically, outer U-shaped support arm 3086A may be coupled to anintermediate U-shaped support arm 3088A via a connector 3087A andintermediate U-shaped support arm 3088A may be coupled to an innerU-shaped support arm 3092A via a connector 3089A. Connectors 3087A,3089A may have the same flared V-shaped configuration as connector 2787Adescribed above. Due to the curved or flared legs of connectors 3087A,3089A, the distance or space between the peaks of adjacent U-shapedsupport arms may be adjustable and allowed to change as described withrespect to connector 2787A.

FIG. 31 illustrates valve prosthesis 3100 in accordance with anembodiment hereof. Valve prosthesis 3100 may include frame 3110 havingan inflow portion 3102 and an outflow portion 3104. Outflow portions insome embodiments may also be considered central or valve-retainingtubular portions of frames thereof. Inflow portion 3102 and outflowportion 3104 of valve prosthesis 3100 may have various configurations,for example, those disclosed in U.S. application Ser. No. 13/736,460,which is incorporated by reference herein in its entirety. Valvecomponent 3120 having leaflets 3124 may be secured within an interior offrame 3110. Although not shown in every embodiment, a valve body orcomponent as described herein may be included in each of the followingembodiments.

As shown in FIG. 31, valve prosthesis 3100 may include a support arm3106 having inner support arm 3188 and outer support arm 3186. Incertain embodiments, inner support arm 3188 and outer support arm 3186may be connected to and extend from frame 3110, or may be integrallyformed as part of frame 3110. Outer support arm 3186 may include sidesegments 3180 and curved middle segment 3184 extending between sidesegments 3180. Inner support arm 3188 may include side segments 3182. Incertain embodiments, inner support arm 3188 may also include a middlesegment (not shown), which may extend between side segments 3182. Frame3110, inner support arm 3188, and outer support arm 3186 may each bemade of suitable bio-compatible materials, for example, but not limitedto, metals such as stainless steel and/or nitinol. It should be notedthat certain embodiments disclosed herein illustrate dual support arms,which can improve fatigue performance, such as shown in FIG. 31 by wayof inner support arm 3188 and outer support arm 3186. Certainembodiments illustrate only a single support arm. It is understood thatone or more support arms can be substituted across various embodimentsdisclosed herein and the illustrated embodiments are not limited to thenumber or configuration of support arms illustrated in each figure. Incertain embodiments, support arms can be symmetrical or asymmetrical.The support arms can be of any suitable length, and the angle betweenthe support arm and the frame can be any angle up to and including 180degrees. As shown, for example, in FIG. 31, in certain embodiments, oneor more crowns along frame 3110 can be located between the side segmentsof the support arms.

Although not shown in FIG. 31, the embodiments disclosed herein mayinclude a tent portion (e.g., tent portion 3240 in FIGS. 32A and 32B).The tent portion can be made of any suitable material, such as, but notlimited to, native or artificial valve tissue, fabric, mesh, and/orelastic materials. In certain embodiments, the tent portion can be aknitted PTFE fabric. In certain embodiments, the tent portion can beconnected in various configurations to any or all of frame 3110, innersupport arm 3188, outer support arm 3186, or any other part of valveprosthesis 3100. The tent portion can be attached by any suitable means,for example, with sutures. The tent portion can provide cushioning forthe native chordae in order to reduce or eliminate direct contactbetween the support arm and chordae. The tent portion can distribute thetension and load placed on the chordae and reduce or eliminate therelative motion of the chordae and friction imparted to the chordae byproviding a forgiving contact surface for the chordae.

FIGS. 32A and 32B illustrate valve prosthesis 3200 in accordance with anembodiment hereof. As shown, valve prosthesis 3200 may include frame3210 having inflow portion 3202 and outflow portion 3204. Valvecomponent 3220 may have leaflets secured within an interior of frame3210. Frame 3210 may include dual support arm 3206 having inner supportarm 3288 and outer support arm 3286. Inner support arm 3288 may includeside segments 3282, which can run generally in a direction of alongitudinal axis of frame 3210. In certain embodiments, inner supportarm 3288 may include curved portions along its length. Outer support arm3286 may include side segments 3280 and middle segment 3284 between sidesegments 3280. In certain embodiments, outer support arm 3286 caninclude curved portions along its length.

Valve prosthesis 3200 may also include tent portion 3240, which can beattached at various locations to frame 3210, inner support arm 3288,and/or outer support arm 3286. As shown in FIG. 32A, in certainembodiments, side segment 3282 of inner support arm 3288 can connect toside segment 3280 of outer support arm 3286. In certain embodiments,side segment 3282 of inner support arm 3288 can connect to middlesegment 3284 of outer support arm 3286. As shown in FIG. 32B, in certainembodiments, tent portion 3240 can be connected to frame 3210, innersupport arm 3288, and outer support arm 3286 in such a way to leave agap G between tent portion 3240 and a curved portion of outer supportarm 3286 near a connection area with outflow portion 3204 of frame 3210.Attaching tent portion 3240 in this manner can create a taut pocket 3244within which the native chordae may be suspended or cradled.

FIGS. 33A and 33B illustrate valve prosthesis 3300 in accordance with anembodiment hereof. Valve prosthesis 3300 may include similar features asdescribed with respect to the embodiment of FIGS. 32A and 32B. Valveprosthesis 3300 may include frame 3310 having inflow portion 3302 andoutflow portion 3304. Valve prosthesis 3300 may also include valvecomponent 3320 having leaflets 324. Valve prosthesis 3300 may include asupport arm 3306 having inner support arm 3388 having side segments3382, which can attach to frame 3310 and/or outer support arm 3386.Outer support arm 3386 can include side segments 3380 and middle segment3384. Valve prosthesis 3300 also can include tent portion 3340, whichcan be connected to frame 3310, inner support arm 3388, and/or outersupport arm 3386.

In certain embodiments, tent portion 3340 can include flap 3396. Flap3396 can extend to either side of outer support arm 3386. Flap 3396 canbe an excess of material of tent portion 3340, and can be free to bendand flex as tension is placed on it from chordae tendinae (CT). Asshown, for example, in FIG. 33B, chordae (CT) can rest within pocket3344 of tent portion 3340. Tension placed upon chordae (CT) can resultin flap 3396 bending or flexing to accommodate the tension, which canprevent chordae (CT) from rubbing against frame 3310 and/or innersupport arm 3388 and outer support arm 3386 of valve prosthesis 3300. Inthis manner, flap 3396 can divert chordae (CT) away from inner supportarm 3388 and outer support arm 3386. In certain embodiments, anadditional strip of material can be attached from a corner of flap 3396to outer support arm 3386 to provide additional support for chordae(CT).

FIGS. 34A and 34B illustrate valve prosthesis 3400 in accordance with anembodiment hereof. As shown, valve prosthesis 3400 may include aU-shaped support arm 3406, as described in previous embodiments hereofand not inner and outer support arms. Valve prosthesis 3400 may includeframe 3410 having inflow portion 3402 and outflow portion 3404, alongwith valve component 3420 having leaflets 3424. As shown in FIGS. 34Aand 34B, support arm 3406 may include side segments 3480 and middlesegment 3484. In certain embodiments side segments 3480 may be closertogether or further apart, creating a narrower or wider support arm3406. In certain embodiments, middle segment 3484 can runperpendicularly across/between side segments 3480, or middle segment3484 can have a curved “U” shape. In certain embodiments, side segmentscan be closer together near outflow end 3405 and further apart nearinflow end 3403. Additional shapes and curvatures of support arm 3406are contemplated.

Tent portion 3440 may be connected to frame 3410 and/or support arm3406, for example, by sutures 3442. Tent portion 3440 may include flap3496, which can be attached to frame 4410. This can prevent flap 3496from bending and flexing as depicted in FIGS. 33A and 33B, which cancause pocket 3444 to be taut between frame 3410 and support arm 3406.Flap 3496 can be various shapes; for example, flap 3496 can berectangular or diamond-shaped. Chordae (CT) can rest within the tautpocket 3444 between support arm 3406 and frame 3410 of valve prosthesis3400. As shown, this can cause chordae (CT) to interact only with pocket3444 of tent portion 3440, without contacting frame 3410 or support arm3406.

FIG. 35 illustrates valve prosthesis 3400, which is the same as theembodiment shown in FIG. 34A. FIG. 35 illustrates angle A created bytent portion 3440 between frame 3410 of outflow portion 3404 and sidesegment 3486 of support arm 3406. Depending on the size, shape, andconfiguration of support arm 3406, angle A can be increased ordecreased.

FIGS. 36A and 36B illustrate valve prosthesis 3600 in accordance with anembodiment hereof. Valve prosthesis 3600 may include frame 3610, inflowportion 3602, and outflow portion 3604. As shown, support arm 3606 has alarger, wider, “U”-shaped configuration in comparison to the embodimentshown in FIGS. 34A and 34B. Side segments 3680 can be generally parallelto a longitudinal axis of valve prosthesis 3600 and middle segment 3684can have a generally curved “U” shape. Tent portion 3640 can beconnected between support arm 3606 and frame 3610, creating angle Abetween frame 3610 and support arm 3606. FIG. 36B shows chordae (CT)within pocket 3644 created by tent portion 3640 extending betweensupport arm 3606 and frame 3610. The wider design of support arm 3606can facilitate implantation of prosthesis 3600.

FIGS. 37A and 37B illustrate valve prosthesis 3700 in accordance with anembodiment hereof. Valve prosthesis 3700 may include frame 3710 havinginflow portion 3702 and outflow portion 3704. Valve prosthesis 3700 mayinclude a support arm 3706 having inner support arm 3788 and outersupport arm 3786. As shown, side segment 3782 of inner support arm 3788may be connected to side segment 3780 of outer support arm 3786 in amanner to create a space between inner support arm 3788 and outersupport arm 3786. Side segments 3780 of outer support arm 3786 may beconnected by middle segment 3784 that extends therebetween. Angle A canbe created between outflow portion 3704 of frame 3710 and outer supportarm 3786. As shown in FIG. 37B, chordae (CT) can rest within pocket 3744created by tent portion 3740. As also shown in side view of FIG. 37B, incertain embodiments, side segment 3782 of inner support arm 3788 can becurved away from frame 3710 of valve prosthesis 3700.

FIGS. 38A and 38B illustrate valve prosthesis 3800 in accordance with anembodiment hereof. Valve prosthesis 3800 may include frame 3810 havinginflow portion 3802 and outflow or central portion 3804. Valveprosthesis 3800 may include a support arm 3806 having dual support arms,i.e., inner support arm 3888 and outer support arm 3886. Outer supportarm 3886 may include side segments 3880 connected by middle segment 3884that extends therebetween. As shown, side segment 3882 of inner supportarm 3888 can run generally parallel to a longitudinal axis of valveprosthesis 3800 and connect to outer support arm 3886 near an end ofmiddle segment 3884. This can create a narrower space between innersupport arm 3888 and outer support arm 3886 in comparison to theembodiment shown in FIGS. 37A and 37B. Angle A can be created betweenframe 3810 and outer support arm 3886. As shown in FIG. 38B, chordae(CT) can rest within pocket 3844 created by tent portion 3840.

FIGS. 39A and 39B illustrate valve prosthesis 3900 in accordance with anembodiment hereof. Valve prosthesis 3900 may include frame 3910 havinginflow portion 3902 and outflow portion 3904. Valve prosthesis 3900 mayinclude support arm 3906 having a dual support arm construction, i.e.,inner support arm 3988 and outer support arm 3986. Outer support arm3986 may include side segments 3980 connected by middle segment 3984that extends therebetween. As shown, side segments 3982 of inner supportarm 3988 may be configured as generally “C” shaped. As shown in FIG.39A, side segments 3982 of inner support arm 3988 may curve inwardlytoward each other as they approach middle segment 3984 of outer supportarm 3986. Side segments 3982 can then curve outward and away from middlesegment 3984 to connect with side segments 3980 of outer support arm3986. Angle A can be created between frame 3910 and outer support arm3986. As shown in FIG. 39B, chordae (CT) can fit within pocket 3944created by tent portion 3940 extending between frame 3910 and outersupport arm 3986.

FIGS. 40A and 40B illustrate valve prosthesis 4000 in accordance with anembodiment hereof. Valve prosthesis 4000 may include frame 4010 havinginflow portion 40002 and outflow portion 40046. As shown in FIG. 40A,valve prosthesis 4000 may have a support arm 4006 that includes innersupport arm 4088 and outer support arm 4086. Outer support arm 4086includes side segments 4080 connected by middle segment 4084 thatextends therebetween. Side segment 4082 of inner support arm 4088 can begenerally parallel to a longitudinal axis of valve prosthesis 4000 andconnect to outer support arm 4086 near middle segment 4084. Angle A canbe created between frame 4010 and outer support arm 4086. As shown inthe side view of FIG. 40B, chordae (CT) can rest within pocket 4044created by tent portion 4040 extending between frame 4010 and outersupport arm 4086 of valve prosthesis 4000.

FIG. 41 illustrates valve prosthesis 4100 in accordance with anembodiment hereof. Valve prosthesis 4100 may include frame 4110, inflowportion 4102, and outflow portion 4104. Valve prosthesis 4100 may have asupport arm 4106 that includes inner support arm 4188 having sidesegment 4182 and outer support arm 4186 having side segment 4180 andmiddle segment 4184. In certain embodiments, a sleeve 4177 may bewrapped around outer support arm 4186 and/or inner support arm 4188 suchthat chordae (CT) interacts or engages with sleeve 4177 rather thansupport arm 4106 or frame 4110 of valve prosthesis 4100. In certainembodiments, sleeve 4177 can be made from the same material as describedfor tent portions in accordance herewith. In certain embodiments, sleeve4177 can be a single piece of fabric that can be wrapped around, forexample, side segment 4180 of outer support arm 4186 and suturedtogether. In certain embodiments, sleeve material may be longitudinallyand/or spirally wrapped around support arm. Sleeve 4177 can be looselyattached to allow relative motion between sleeve 4177 and outer supportarm 4186 to prevent friction with chordae (CT), such that sleeve 4177can slide on side segment 4180 of outer support arm 4186. In someembodiments, the sleeve 4177 may include one or more materials and/ormethods that can reduce friction between the support arm and the sleeveand/or the chordae and the sleeve, including but not limited to, thesleeve being designed to be able to roll over the support arm, or thesleeve being designed to be able to slide across the support arm, or thesleeve comprising a material with a low shear modulus that can deform toabsorb any motion, for example caused by the chordae acting on thesleeve. In some embodiments, the sleeve may include a fluid, such assaline, filled balloon or sac that can absorb any motion, for examplecaused by the chordae acting on the sleeve. In some embodiments, asupport arm may comprise a tent-like member. In some embodiments, asupport arm may include a covering of graft material.

FIGS. 42A and 42B illustrate valve prosthesis 4200 in accordance with anembodiment hereof. Valve prosthesis 4200 may include frame 4210 and afirst support arm 4299, and a second support arm 4206. First support arm4299 may include barb 4298, which can facilitate anchoring valveprosthesis 4200 in the native valve. Second support arm 4206 may includeside portion 4280, middle portion 4284, and inner portion 4288. It iscontemplated that side portion 4280, middle portion 4284, and innerportion 4288 may have various curvatures and may connect with each otherin various locations. In certain embodiments, valve prosthesis 4200 caninclude a covering, for example a mesh fabric, similar to the tentportion described above. In some embodiments, during delivery of valveprosthesis 4200 to the native valve and as shown in FIG. 42A, secondsupport arm 4206 may be distally-facing or extending from outflow ordistal end 4205 and first support arm 4299 may be proximally-facing. Insome embodiments, upon being released from a delivery device as shown inFIG. 42B, second support arm 4206 can fold proximally toward proximal orinflow end 4203, so as to trap a native leaflet between first supportarm 4299 and second support arm 4206. In some embodiments, duringdelivery of valve prosthesis 4200 to the native valve both first supportarm 4299 and second support arm 4206 may be distally-facing or extendingfrom outflow or distal end 4205. Depending on the delivery device used,for example a single sheath delivery device vs. a multi-sheath deliverydevice, and/or the orientation of valve prosthesis 4200 within thedelivery device, second support arm 4206 may be released from thedelivery device prior to the release of first support arm 4299 or firstsupport arm 4299 may be released prior to the release of second supportarm 4206. In some embodiments, following delivery of valve prosthesisfirst support arm 4299 and second support arm 4206 may be configured totrap, engage, capture, clamp, pin, and/or pinch a native leaflet betweenthe support arms and/or support arm 4299 and support arm 4206 may beconfigured to trap, engage, capture, clamp, pin, and/or pinch chordaebetween the support arms and/or support arm 4299 and support arm 4206may be configured to trap, engage, capture, clamp, pin, and/or pinch oneor more leaflets and/or chordae between one or more support arms and thevalve prosthesis frame. FIG. 43 illustrates valve prosthesis 4300 inaccordance with an embodiment hereof. In certain embodiments, engagementor support arms 4306Aa, 4306B are coupled to one another by ring or bar4397 that at least partially surrounds valve frame 4310, so as to trapthe native leaflets. In certain embodiments, ring or bar 4397 may beshaped to define groove 4397A, so as to hold or contain native chordaewithin groove 4397A.

FIG. 44 illustrates a side view of a valve prosthesis 4400 in accordancewith an embodiment hereof in an expanded or deployed configuration,before being loaded into and after release from its compressedconfiguration within a delivery system 4430 as shown in FIGS. 44A and44B. FIGS. 44A and 44B illustrate side and end views, respectively, ofvalve prosthesis 4400 of FIG. 44 in an unexpanded or compressed deliveryconfiguration loaded into delivery 4430 system in accordance with anembodiment hereof. As described above, each support arm of valveprosthesis in accordance herewith may rotate and transform from adistally-extending compressed configuration to a proximally-extendingdeployed configuration. With reference to the exemplary valve prosthesis4400 in FIG. 44, valve prosthesis 4400 may include a tubular frame orstent 4410 that is similar to the frames described above, a valvecomponent (not shown in FIGS. 44, 44A, 44B and 45A-44E for simplicity ofillustration) attached within the interior portion of frame 4410, andtwo positioning elements or support arms 4406. In a compressed ordelivery configuration, each support arms 4406 may be approximatelyparallel with a longitudinal axis L_(a) of frame 4410 and may distallyextend from a distal or outflow end 4405 of frame 4410. Delivery system4430 may include a catheter 4433 and an outer retractable sheath or tube4434. Valve prosthesis 4400 may be mounted over an inner shaft 4436 ofcatheter 4433 at the distal end thereof and sheath 4434 may surround andconstrain valve prosthesis 4400 in a compressed configuration. In oneembodiment, catheter 4433 may also include a retainer 4438 whichtemporarily secures proximal or inflow end 4403 of frame 4410 ontocatheter 4433. For example, retainer 4438 may include an end stentcapture configuration as described in U.S. Patent Pub. No. 2009/0276027to Glynn, which is incorporated by reference herein in its entirety.

FIGS. 45A-45E illustrate progressive side views of valve prosthesis 4400loaded within a delivery system 4430, wherein sheath 4434 of deliverysystem 4430 is progressively proximally retracted to release valveprosthesis 4400 therefrom. In order to begin deployment of valveprosthesis 4400, sheath 4434 may be retracted in a proximal direction toexpose and release support arms 4406 as shown in FIG. 45A. Upon initialrelease from sheath 4434, support arms 4406 flare or spread outwardlyfrom the distal end 4405 of frame 4410 such that support arms 4406 forman acute angle Ø with respect to longitudinal axis L_(A).

As sheath 4434 is further retracted, support arms 4406 continue to beexposed and continue to bend backwards towards the outer surface ofsheath 4434 and frame 4410. Notably, as support arms 4406 are releasedfrom sheath 4434, frame 4410 remains constrained within sheath 4434.FIG. 45B illustrates support arms 4406 approaching a transversereference axis TA between an initial distally-extending compressedconfiguration and a final proximally-extending deployed configuration.Transverse reference axis T_(A) as utilized herein describes animaginary reference line that extends approximately ninety degrees orperpendicular to the longitudinal axis L_(A) of frame 4410. FIG. 45Cillustrates support arms 4406 after passing over the transversereference axis T_(A), with support arms 4406 fully exposed or releasedfrom sheath 4434 while frame 4410 is still compressed within sheath4434. One particular feature of support arms 4406 is apparent whencomparing FIGS. 45B and 45C. Support arms 4406 may bend or curvegradually backwards such that distal portions or tips 4431A of supportarms 4406 may pass over the transverse reference axis TA before proximalportions or bases 4431B of support arms 4406. After distal tips 4431A ofsupport arms 4406 pass or cross over the transverse reference axis TAand are pointing in a proximal direction, proximal bases 4431B ofsupport arms 4406 approach the transverse reference axis TA as shown inFIG. 10. Stated another way, distal tips 4431A of each support arm 4406may bend past transverse reference axis TA prior to proximal bases 4431Bof each support arm 4406. Due to the above-described flaring orexpanding sequence in which support arms 4406 curve backward, the lengthof support arms 4406 may be greater than if both the proximal and distalportions of the support arms crossed over the transverse reference axisTA at the same time, i.e., if the support arms were straight andextended generally parallel to the transverse reference axis TA duringdeployment. In addition, since frame 4410 is still compressed withinsheath 4434, it can be observed that the length of support arms 4406 maybe greater than if frame 4410 was released from sheath 4434 and in adeployed configuration. Accordingly, the length of support arms 4406 ismaximized which increases their ability to anchor valve prosthesis 4400when it is positioned to replace a valve. In an embodiment in whichvalve prosthesis 4400 is positioned at a mitral valve, the length ofeach support arm 4406 may be between 10 and 12 mm.

FIGS. 45D and 45E illustrate a continued deployment of valve prosthesis4400. Sheath 4434 continues to be proximally retracted, exposingself-expanding frame 4410 such that frame 4410 is released to assume adeployed configuration. Sheath 4434 is proximally retracted untilproximal or inflow end 4403 of frame 4410 is exposed and allowed toself-expand, thereby uncoupling from retaining tip 4438 of catheter4433. FIG. 44 illustrates a final deployed configuration of valveprosthesis 4400, in which each support arm 4406 proximally extends fromdistal or outflow end 4405 of frame 4410. As previously described, thebackwards rotation that may occur during deployment may result in eachsupport arm 4406 translating more than ninety degrees from a compressed,delivery configuration. During deployment, each support arm 4406 mayessentially deploy or translate in an arc path that may extend between90 and 180 degrees from an initial compressed configuration and a finaldeployed configuration. In the embodiment of FIG. 44 shown ex vivo, eachsupport arm 4406 may be bent or rotated approximately 180 degreesbetween an initial distally-extending compressed configuration shown inFIG. 44A and a final proximally-extending deployed configuration showntherein. However, when positioned in vivo, tissue such as native valveleaflets may be sandwiched between each support arm 4406 and the outersurface of frame 4410 and as a result, the total rotation or bending ofsupport arms 4406 in a final deployed configuration may be less than 180degrees with respect to an initial distally-extending compressedconfiguration.

Rotating from an initial distally-extending configuration to a finalproximally-extending configuration allows valve prosthesis 4400 to bedeployed in the annulus of a native valve, such as a mitral valve,rather than the outflow side of a native valve, thereby minimizing thelength which the prosthesis and the delivery system protrudes into aheart chamber, such as the left ventricle.

In some embodiments, the support arms and frame may be deployable viaone delivery sheath. In other embodiments, the support arms and frameare deployable via more than one delivery sheath. In one embodiment, afirst distal cone or delivery sheath may be distally advanced duringdeployment to deploy the support arms and then a second proximaldelivery sheath may be proximally retracted to deploy the frame. In oneembodiment, a first proximal delivery sheath may be proximally advancedduring deployment to deploy the support arms and then a second distaldelivery cone or sheath may be distally retracted to deploy the frame.For example, the ENGAGER delivery system from Medtronic, Inc. ofMinneapolis, Minn. is a valve prosthesis delivery system that deploys avalve prosthesis in this manner and may be adapted for use withembodiments hereof. In accordance with embodiments hereof, valveprosthesis delivery systems and methods disclosed in U.S. Pat. Appl.Pub. No. 2008/0071361 to Tuval et al. and U.S. Pat. Appl. Pub. No.2010/0100167 to Bortlein et al., each of which is incorporated byreference herein in its entirety, that deploy a valve prosthesisutilizing multiple, split, and/or dual sheaths or delivery catheters maybe adapted for use with embodiments hereof.

In order to transform between the initial distally-extending compressedconfiguration and the final proximally-extending deployed configuration,support arms or positioning elements according to some embodimentsdescribed herein are formed from a self-expanding material that has amechanical memory to return to the proximally-extending deployedconfiguration as discussed further below.

FIGS. 46A-46E illustrate a method of implanting a valve prosthesis 4600in accordance with an embodiment hereof to perform a heart valvereplacement procedure, and more particularly a mitral valve replacement,with minimal blood flow stoppage or interruption. FIG. 46A illustrates aportion of a heart (H) including a left atrium (LA), a left ventricle(LV), a mitral valve (MV) and an aortic valve (AV). Blood flow (BF) isdepicted with directional arrows in FIG. 46A in the left atrium (LA),into left ventricle (LV) through mitral valve (MV), and into the aortathrough aortic valve (AV). When the native mitral valve is operatingproperly, the native leaflets will generally function in such a way thatblood flows toward the left ventricle (LV) when the leaflets are in anopen position, and so that blood is prevented from moving toward or intothe left atrium (LA) when the leaflets are in a closed position. A valveprosthesis 4600 in accordance with an embodiment hereof may bepositioned in the area of mitral valve (MV) when the native valve is notfunctioning properly, i.e., to replace the mitral valve, in accordancewith the invention, thereby pushing the native leaflets away from theblood flow path.

With reference to FIG. 46A, a prosthetic valve delivery system 4630 isshown after having been introduced into the vasculature via apercutaneous entry point, such as the Seldinger technique, and havingbeen tracked through the vasculature and into the left atrium so thatdistal tip 4630A is positioned proximate the mitral valve. For example,the percutaneous entry point may be formed in a femoral vein.Thereafter, a guidewire (not shown) is advanced through the circulatorysystem, eventually arriving at the heart. The guidewire is directed intothe right atrium, traverses the right atrium and is made to puncturewith the aid of a transeptal needle or pre-existing hole, the atrialseptum, thereby entering the left atrium. Once the guidewire ispositioned, the endoluminal entry port and the atrial septum are dilatedto permit entry of a guide catheter (not shown) and/or prosthetic valvedelivery system 4630 into the left atrium. Thereafter, prosthetic valvedelivery system 4630 is advanced into the left atrium through thepunctured atrial septum and positioned proximate to the mitral valve(MV). Although not shown, it will be understood by those of ordinaryskill in the art that prosthetic valve delivery system 4630 may beinserted into a guide catheter in order to be advanced to a positionproximate to the mitral valve (MV). In addition, although described as atransfemoral antegrade approach for percutaneously accessing the mitralvalve, the valve prosthesis 4600 may be positioned within the desiredarea of the heart via entry other different methods such as atransseptal antegrade approach via a thoracotomy or a transatrialantegrade approach via a thoracotomy for accessing the mitral valve.

Similar to delivery system 4430 described above with respect to FIGS.44A, 44B and 45A-45E, prosthetic valve delivery system 4630 includes anouter retractable sheath or tube 4634 positioned over the a catheter(not shown in FIGS. 46A-46E) having compressed valve prosthesis 4600 tokeep it from expanding and to minimize interference between the valveprosthesis and the vasculature through which it will be traveling. Valveprosthesis 4600 is mounted over an inner shaft of the catheter at thedistal end thereof and sheath 4634 surrounds and constrains valveprosthesis 4600 in the compressed configuration. After being advancedinto the left atrium (LA), prosthetic valve delivery system 4630including sheath 4634 may then be advanced through the mitral valve (MV)and into the left ventricle (LV) as shown in FIG. 46B. Distal tip 4630Aof prosthetic valve delivery system 4630 is advanced into the leftventricle (LV) until valve prosthesis 4600 is centered at the nativemitral valve, i.e., deployed in the annulus of the native mitral valve,with positioning elements or support arms 4606A, 4606B of valveprosthesis 4600 contained within sheath 4634 and distally extending intothe left ventricle (LV). As previously discussed, deploying valveprosthesis 4600 in the middle of the native valve rather than theoutflow side of the native mitral valve minimizes the length which theprosthesis and the delivery system protrudes into the left ventricle.

Referring now to FIG. 46C, when valve prosthesis 4600 is in position inthe middle of the native mitral valve, support arms 4606A, 4606B ofvalve prosthesis 4600 are released by retracting sheath 4634 ofprosthetic valve delivery system 4630 by a sufficient amount that thisportion of the prosthesis is exposed. Due to the self-expandingproperties of the support arms, support arms 4606A, 4606B will expandradially outwardly relative to the sheath in which it was enclosed. Asshown FIG. 46C, and also referring to FIG. 45A described above, uponinitial release from sheath 4634, support arms 4606A, 4606B flare orspread outwardly from the outer surface of the remainder of theprosthesis such that support arms 4606A, 4606B are acutely angled withrespect to longitudinal axis L_(A). During the transformation betweenthe distally-extending compressed configuration and theproximally-extending deployed configuration, support arms 4606A, 4606Bare located on outflow side, i.e., the left ventricle (LV) side, of themitral valve while stent or frame 4610 of prosthesis 4600 is positionedwithin the mitral valve and still contained within sheath 4634.

Exposure and rotation of support arms 4606A, 4606B continues as sheath4634 is retracted. FIG. 46D illustrates support arms 4606A, 4606B fullyexposed or released from sheath 4634 while stent 102 is still compressedwithin sheath 4634. Support arms 4606A, 4606B are now proximallyextending, such that they firmly press against the native mitral valveleaflets and/or the left ventricle (LV) in order to position valveprosthesis 4600.

After support arms 4606A, 4606B are deployed to position, anchor and/orhold valve prosthesis 4600 in place as desired, sheath 4634 continues tobe proximally retracted, exposing self-expanding frame 4610 such thatthe frame and the entire valve prosthesis is released from the deliverysystem to assume its deployed configuration. Due to the self-expandingproperties of the stent frame, frame 4610 will expand outwardly relativeto the sheath in which it was enclosed. Sheath 4634 is proximallyretracted until the proximal end of frame 4610 is exposed and allowed toself-expand, thereby uncoupling mitral valve prosthesis 4600 fromdelivery system 4630. The delivery system 4630 can then be retractedfrom the patient, leaving the expanded mitral valve prosthesis 4600deployed at the mitral valve as shown in FIG. 46E. In the final deployedconfiguration of valve prosthesis 4600, each support arm 4606A, 4606Bproximally extends from a distal or outflow end 4605 of frame 4610. Eachsupport arm 4606A, 4606B rotates in a radial direction between 90 and180 degrees from the initial distally-extending compressed configurationto the final proximally-extending deployed configuration until thesupport arms 4606A, 4606B firmly press against the native mitral valveleaflets and/or the left ventricle (LV) in order to properly positionmitral valve prosthesis 4600. The amount or degree of rotation maydepend upon a patient's individual anatomy and state of the nativemitral valve leaflets.

FIG. 47 is a side view of a valve prosthesis 4700 having inflow orcommissural support arms 4771 in accordance with an embodiment hereof.Valve prosthesis 4700 is shown in an expanded or deployed configurationin FIG. 47. Valve prosthesis 4700 has an inflow portion 4702 and anoutflow or central portion 4704 that holds a prosthetic valve component4720 that is capable of blocking flow in one direction to regulate flowthrough valve prosthesis 4700, as similarly described in previousembodiments. Valve prosthesis 4700 includes a self-expanding frame,framework or stent 4710 that defines the inflow and outflow portions4702, 4704 and includes a pair of support arms 4706A, 4706B that extendfrom a distal end 4705 thereof. A pair of commissural engagement supportarms 4771 also extend from distal end 4705 of frame 4710 and may be anintegral part thereof. In the embodiment shown in FIG. 47, the pair ofcommissural engagement support arms 4771 includes two U-shaped supportarms that are side-by-side and positioned along the circumference ofcentral portion 4704 approximately half way between the main supportarms 4706A, 4706B. In an embodiment, another pair of commissuralengagement support arms is also located at a diametrically opposedlocation of frame 4710 from the pair of commissural engagement supportarms 4771 shown in FIG. 47. Support arms 4706A, 4706B enable nativeleaflet capture during deployment as described above. However, theadditional commissural engagement support arms 4771 are not intended tocapture the native leaflets but instead are configured to push againstthe ventricular side of the mitral valve annulus to aid in securing andsealing of the valve prosthesis within the native valve. In someembodiments, valve prosthesis may comprise one or more leafletengagement support arms and/or one or more commissural support arms.Commissural or annulus engagement support arms may comprise a variety ofshapes, sizes, geometries, and/or configurations as previously describedfor leaflet engagement support arms and/or chordae engagement supportarms. Commissural or annulus engagement support arms are designed orconfigured to press against the ventricular portion of the native valveannulus with a sufficient force to prevent or minimize valve prosthesismovement and/or migration, for example migration into the left atrium.Commissural or annulus engagement support arms may or may not compriseone or more anchors or barbs.

FIG. 47A is a side sectional view of a distal portion of a deliverysystem 4730 with valve prosthesis 4700 in a partially deployedconfiguration, in accordance with an embodiment hereof. A proximal orinflow end 4703 of frame 4710 is held by an inner shaft or tubularmember 4736 of delivery system 4730 and the inflow and outflow portions4702, 4704 of frame 4710 are held in a compressed configuration by asheath or outer tubular member 4734 of delivery system 4730. Supportarms 4706A, 4706B and commissural engagement support arms 4771 areloaded in a straightened configuration, as shown in FIG. 47A, such thatall extend distally from distal or outflow end 4705 of frame 4710. Moreparticularly, distal ends or tips 4731 a, 4731B of commissuralengagement support arms 4771 are held within a distal cone or tip 4730Aof the delivery system 4730. During implantation, sheath 4734 ofdelivery system 4730 is proximally drawn back, exposing support arms4706A, 4706B, such that the main support arms 4706A, 4706B may capturethe native leaflets as described in detail above. As shown in FIG. 47A,the pair of commissural engagement support arms 4771 is stillconstrained in the straight, un-deployed configuration at this step.Once leaflet capture is verified, the distal cone 4731A is advanced, orother tip capture mechanism is manipulated, to release the commissuralengagement support arms 4771. The embodiment of FIG. 47 is intended toeliminate or minimize complications of chordae entanglement with thecommissural support arms and yet still provide additional sealing forcesby pushing on the ventricular side of the mitral valve annulus with thecommissural engagement support arms 4771 by pinching the annulus betweencommissural engagement support arms 4771 and the inflow portion 4702 offrame 4710 of valve prosthesis 4700.

FIG. 48 is a side view of a valve prosthesis 4800 having commissuralanchors 4861 in accordance with an embodiment hereof. Valve prosthesis4800 is shown in an expanded or deployed configuration in FIG. 48. Valveprosthesis 4800 has an inflow portion 4802 and an outflow or centralportion 4804 that holds a prosthetic valve component 4820 that iscapable of blocking flow in one direction to regulate flow through valveprosthesis 4800, as similarly described in previous embodiments. Valveprosthesis 4800 includes a self-expanding frame, framework or stent 4810that defines the inflow and outflow portions 4802, 4804 and includes apair of support arms 4806A, 4806B that extend from a distal end 4805thereof. Support arms 4806A, 4806B enable native leaflet capture duringdeployment as described above. A plurality of commissural anchors 4861,two of which are shown in FIGS. 48 and 48B, downwardly extend andinwardly curve from inflow portion 4802 of frame 4810 and may be anintegral part thereof. In the embodiment shown in FIG. 48, thecommissural anchors 4861 may be described as hook-shaped and may beevenly spaced about a circumference of inflow portion 4802. In someembodiments, commissural anchors 4861 may be concentrated in specificlocations around the circumference of the inflow portion of the valveprosthesis, such as the commissure regions of the native valve annulus.

FIG. 48A is a side sectional view of a distal portion of a deliverysystem 4830 with valve prosthesis 4800 in a partially deployedconfiguration, in accordance with an embodiment hereof. When valveprosthesis 4800 is held in a compressed, loaded configuration withindelivery system 4830, sutures 4842 constrain commissural anchors 4861 ina straight configuration. Other methods of constraining anchors 4861 ina straight configuration may include, for example, the use of a rigidsleeve or tube that would pull away from the anchors upon deployment ofthe valve prosthesis. In some embodiments, the suture or sleeve materialmay comprise a biodegradable material thereby delaying the release ordeployment of the anchors until at a point in time followingimplantation that corresponding to the degradation rate of thebiodegradable material used. With reference to FIG. 48A, a proximal orinflow end 4803 of frame 4810 and commissural anchors 4861 are attachedby sutures 4842 to an inner shaft or tubular member 4836 of deliverysystem 4830 after outflow portion 4804 and support arms 4806A, 4806B offrame 4810 have been deployed from sheath or outer tubular member 4834of delivery system 4830. Accordingly, valve prosthesis 4800 is implantedusing the basic procedure described above, with support arms 4806A,4806B being deployed to capture the native leaflets and thereaftercentral portion 4804 with the valve component secured therein and theinflow portion 4802 would be allowed to expand. However, a controlledlengthening of sutures 4842 of delivery system 4830 coincides with theexpansion of inflow portion 4802 of frame 4810 as shown in FIG. 48A,such that inflow portion 4802 is expanded but still attached to deliverysystem 4830 via sutures 4842. At this juncture a clinician can assessthe prosthetic valve's function and any complications, such asparavalvular leakage. In the partially deployed configuration of FIG.48A, the sutures 4842 will keep the commissural anchors 4861 in thestraightened configuration. If the clinician approves of the prostheticvalve's performance, the sutures 4842 are released. Without the sutures4842 constraining the commissural anchors 4861, they will bend intotheir un-deformed, pre-set positions and pierce the tissue to anchor theframe 4810 in place. FIG. 48B illustrates valve prosthesis 4800implanted at a mitral valve target location (MV) with commissuralanchors 4861 embedded or anchored within the atrial tissue of the heart.If the clinician does not approve of the prosthetic valve's performanceupon initial implantation, prosthetic valve 4800 may be removed whilethe commissural anchors 4861 are still in the straightened configurationof FIG. 48A, prior to any active fixation, i.e., piercing of the hearttissue. In some embodiments, all of the commissural anchors of valveprosthesis may be oriented in the same direction, for example a radiallyinward direction or a radially outward direction, and/or the commissuralanchors may be oriented in a combination of directions, for example someanchors may be oriented in a radially inward direction while someanchors may be oriented in a radially outward direction. In someembodiments, commissural anchors may comprise one or more hooks,tent-stake-like protrusions, and/or barbs to aid in anchoring, forexample. In some embodiments, such commissural anchors may be deliveredeither with the inflow portion or independent of the inflow portion.

FIG. 49 is a side view of a valve prosthesis 4900 having atrialengagement support arms 4991 in accordance with an embodiment hereof.Valve prosthesis 4900 is shown in an expanded or deployed configurationin FIG. 49. Valve prosthesis 4900 has an inflow portion 4902 havingS-shaped struts as described with reference to various embodiments aboveand an outflow or central portion 4904, which holds a prosthetic valvecomponent (not shown) that is capable of blocking flow in one directionto regulate blood flow through valve prosthesis 4900, as similarlydescribed in previous embodiments. Valve prosthesis 4900 includes aself-expanding frame, framework or stent 4910 that defines the inflowand outflow portions 4902, 4904 and includes a pair of support arms4906A, 4906B that extend from a distal end 4905 thereof. Support arms4906A, 4906B enable native leaflet capture during deployment asdescribed above. A plurality of atrial engagement support arms 4991, twoof which are shown in FIG. 49, extend and curve inwardly from inflowportion 4902 of frame 4910 and may be an integral part thereof. Theatrial engagement support arms may be considered as cantilever elements,wherein each atrial engagement support arm 4991 has a radially outermostend 4991A connected to inflow portion 4902 and an unconnected innermostend 4991B that sits below inflow portion 4902 and radially outward ofcentral portion 4904. In the embodiment shown in FIG. 49, the atrialengagement support arms 4991 may be described as curved beams or struts,and may be evenly spaced about a circumference of inflow portion 4902.

FIGS. 49A and 49B illustrates the valve prosthesis 4900 implanted at amitral valve (MV) target location within a heart in accordance with anembodiment hereof. Valve prosthesis 4900 is implanted using a method asdescribed above, with support arms 4906A, 4906B being deployed tocapture the native leaflets and thereafter central portion 4904 with thevalve component secured therein and the inflow portion 4902 beingallowed to expand and deploy within the mitral valve (MV). However inthe embodiment of FIG. 49 and as shown in FIG. 49A, after initialdeployment within the left atrium (LA), atrial engagement support arms4991 are compressed, or closed between the atrial tissue and theS-shaped struts or primary cantilevers of inflow portion 4902 such thatthey are not readily visible in FIG. 49A. For example, the cantileverelements may initially have the same shape and/or profile as the inflowportion. In the event that over time chordal damage, elongation, or leftventricle (LV) remodeling causes frame 4910 of valve prosthesis 4900 tomove upward or towards the left atrium (LA) as shown in FIG. 49B,decreased loading of inflow portion 4902 of frame 4910 will occur due tothe decrease in tension provided by the chordae tendinae (CT). If overtime the frame 4910 moves upward enough that the primary cantilever ofinflow portion 4902 lifts off of the atrial floor and loses its abilityto seal, the secondary cantilever or atrial engagement support arm 4991will decompress, or open to maintain sealing over a greater amount offrame 4910. Additionally, the secondary cantilever or atrial engagementsupport arm 4991 may be designed to be much more flexible than theprimary cantilever S-shaped struts that form inflow portion 4902. Aswell in another embodiment, a paravalvular leakage skirt (not shown) maybe sewn onto secondary cantilever or atrial engagement support arm 4991,which open towards the radial center of valve prosthesis 4900, to createa pocket around the circumference of inflow portion 4902 such that theatrial engagement support arms 4991 may use the pressure of the blood tohelp seal against the heart anatomy. In another embodiment, aparavalvular leakage skirt covers the atrial engagement support arms andis attached to frame 4900 in such a manner that the formation of apocket around the circumference of the frame is prevented but the skirtstill allows movement of the atrial engagement support arms as describedabove.

FIG. 50 is a side view of a valve prosthesis 5000 having inflow supportarms 5071 in accordance with an embodiment. Valve prosthesis 5000 isshown in an expanded or deployed configuration in FIG. 50. Valveprosthesis 5000 has an inflow portion 5002 and an outflow or centralportion 5004, which holds a prosthetic valve component (not shown) forblocking flow in one direction to regulate blood flow through valveprosthesis 5000, as similarly described in previous embodiments. Valveprosthesis 5000 includes a self-expanding frame, framework or stent 5010that defines the inflow and outflow portions 5002, 5004 and includes apair of support arms 5006A, 5006B that extend from a distal or outflowend 5005 thereof. A pair of inflow support arms 5071A, 5071B extend froma proximal or inflow end 5003 of frame 5010 and may be an integral partthereof. Inflow support arms 5071A, 5071B may alternatively be describedas commissural engagement support arms and/or ventricular engagementsupport arms. Inflow support arms 5071A, 5071B may be located atdiametrically opposed locations of frame 5010 such that each ispositioned along the circumference of valve prosthesis 5000approximately half way between the main support arms 5006A, 5006B. Inthis manner, each inflow support arm 5071A, 5071B will align with arespective commissure of the native mitral valve upon implantation toengage with tissue on the ventricular-side of the prosthesis. In theembodiment of FIG. 50, each inflow support arm 5071A, 5071B has a dualsupport arm construction, as seen more clearly in FIGS. 51D and 51E withrespect to inflow support arm 5071A includes an outer support arm 5086Aand an inner support arm 5088A that is similar to main support arms206A, 206B of frame 210 in the embodiment of FIG. 4. As in theembodiment of FIG. 47, main support arms 5006A, 5006B enable nativeleaflet engagement or capture during deployment as described above andthe additional inflow support arms 5071A, 5071B are configured to engageor push against the ventricular side of the mitral valve annulus to aidin securing and sealing of valve prosthesis 5000 within the nativevalve.

FIGS. 51A, 51B, 51BB, 51C, 51CC, 51D, 51DD, 51E, and 51EE illustrate amethod of implanting valve prosthesis 5000 within a mitral valve (MV) ofa heart in accordance with an embodiment hereof. FIG. 51A is a side viewof a distal portion of a prosthetic valve delivery system 5030 withvalve prosthesis 5000 loaded therein in a compressed deliveryconfiguration, in accordance with an embodiment hereof. Main supportarms 5006A, 5006B and inflow supports arms 5071A, 5071B are held withina sheath 5034 in an unbent or straightened state with the main supportarms 5006A, 5006B extending from outflow end 5005 of central portion5004 and inflow support arms 5071A, 5071B extending from inflow end 5003of central portion 5004. Delivery system 5030 is shown in FIG. 51A afterhaving been advanced into the left atrium (LA), with sheath 5034 havingbeen advanced through the mitral valve (MV) and into the left ventricle(LV) such that a distal tip 5030A of delivery system 5030 is advancedinto the left ventricle (LV) until valve prosthesis 5000 loaded thereinis centered at the native mitral valve (MV).

FIGS. 51B and 51BB depict side views of valve prosthesis 5000 positionedin the middle of the native mitral valve (MV) with main support arms5006A, 5006B of valve prosthesis 5000 released by the proximalretraction sheath 5034. FIG. 51BB is an alternate side view of FIG. 51Brotated 90° clockwise about a longitudinal axis L_(A) thereof from theorientation shown in FIG. 51B. Due to the self-expanding properties ofthe support arms, support arms 5006A, 5006B expand radially outwardlyrelative to the sheath in which they were enclosed and rotate proximallyuntil they each capture their respective native valve leaflet AL, PL.The remainder of frame 5010 and inflow support arms 5071A, 5071B ofvalve prosthesis 5000 are positioned within the mitral valve (MV) butare still contained within sheath 5034.

FIGS. 51C and 51CC depict side views of valve prosthesis 5000 withinflow support arms 5071A, 5071B released by further proximal retractionof sheath 5034. FIG. 51CC is an alternate side view of FIG. 51C rotated90° clockwise about a longitudinal axis L_(A) thereof from theorientation shown in FIG. 51C. Due to the self-expanding properties ofthe support arms, inflow support arms 5071A, 5071B expand radiallyoutwardly relative to the sheath in which they were enclosed.

With continued proximal retraction of sheath 5034 as shown in FIGS. 51Dand 51DD, inflow support arms 5071A, 5071B continue to rotate proximallythrough respective commissures of the native mitral valve (MV) untilthey engage tissue of the left ventricle (LV) on diametrically opposedlocations of the mitral valve annulus (MVA). FIG. 51DD is an alternateside view of FIG. 51D rotated 90° clockwise about a longitudinal axisL_(A) thereof from the orientation shown in FIG. 51D. The remainder offrame 5010 of valve prosthesis 5000 is partially expanded within themitral valve (MV) and the left atrium (L_(A)).

Sheath 5034 is proximally retracted until the proximal or inflow end5003 of frame 5010 is exposed and allowed to self-expand, therebyuncoupling mitral valve prosthesis 5000 from delivery system 5030.Delivery system 5030 can then be retracted from the patient, leaving theexpanded mitral valve prosthesis 5000 deployed at the mitral valve (MV)as shown in FIGS. 51E and 51EE. FIG. 51EE is an alternate side view ofFIG. 51E rotated 90° clockwise about a longitudinal axis L_(A) thereoffrom the orientation shown in FIG. 51E. In the final deployedconfiguration of valve prosthesis 5000, each main support arm 5006A,5006B proximally extends from distal or outflow end 5005 of frame 5010toward the inflow end thereof and each inflow support arms 5071A, 5071Bdistally extends from proximal or inflow end 5003 of frame 5010 towardthe outflow end thereof. The support arms 5006A, 5006B firmly pressagainst the native mitral valve leaflets (AL, PL) and/or tissue of theleft ventricle (LV) in order to properly position mitral valveprosthesis 5000 within the mitral valve annulus (MVA). The inflowsupport arms 5071A, 5071B provide additional sealing forces by pushingon the ventricular side of the mitral valve annulus (MVA) with themitral valve annulus (MVA) being pinched or sandwiched between inflowsupport arms 5071A, 5071B and inflow portion 5002 of frame 5010 of valveprosthesis 5000.

In one or more embodiments, valve prosthesis may comprise an inflowportion, a central portion, and an outflow portion. In one or moreembodiments, the valve prosthesis may comprise a single unitarystructure or the valve prosthesis may comprise one or more components orportions coupled or connected together. In one or more embodiments, thevalve prosthesis may comprise a central portion comprising a valve body,member, or component. In one or more embodiments, the valve body,member, or component may comprise one or more valve leaflets. In one ormore embodiments in accordance herewith, the valve leaflets of the valvebody, member, or component are attached to an upstream end of thecentral portion to extend into an atrial or inflow portion of the frame,and into the left atrium when implanted to replace a mitral valve insitu, such that the valve body, member, or component is not solelylocated on or within the outflow or ventricular portion of the frame,and therefore does not sit only within the left ventricle when implantedto replace a mitral valve in situ. By locating a portion of the valveleaflets in the left atrium, the required length of the central orvalve-retaining tubular portion of the frame is minimized and the lengthof frame that protrudes into the left ventricle may be reduced. In oneor more embodiments, valve member and/or one or more of its componentsmay comprise one or more materials, as described herein.

In one or more embodiments, the central portion and/or one or more ofits components may comprise one or more longitudinal or cross-sectionalshapes, such as a geometric shape, a non-geometric shape, a tubularshape, a cylindrical shape, a circular shape, an elliptical shape, anoval shape, a triangular shape, a rectangular shape, a hexagonal shape,a square shape, an hourglass shape, a polygonal shape, a funnel shape, anozzle shape, a D-shape, a saddle shape, a planar shape, a non-planarshape, a simple geometric shape, and/or a complex geometric shape. Inone or more embodiments, the central portion and/or one or more of itscomponents may comprise one or more fixation elements or members such asanchors, barbs, clips, prongs, grommets, sutures, and/or screws. In oneor more embodiments, the central portion and/or one or more of itscomponents may comprise a frame, a framework, or stent-like structure,as described herein. In one or more embodiments, the outflow portionand/or one or more of its components may comprise, be covered with, becoated with, or be attached or coupled to one or more materials, asdescribed herein. In one or more embodiments, the central portion and/orone or more of its components may comprise one or more support arms,components, or members as described herein. In one or more embodiments,one or more support arms may comprise one or more cantilever componentsor portions. In one or more embodiments, the central portion and/or oneor more of its components, such as one or more support arms, may bedesigned to engage and/or push against the native valve annulus. In oneor more embodiments, the central portion and/or one or more of itscomponents, such as one or more support arms, may be designed to engage,capture, clamp, hold, and/or trap one or more native valve leaflets. Inone or more embodiments, the central portion and/or one or more of itscomponents, such as one or more support arms, may be designed to engage,capture, clamp, hold, and/or trap one or more native chordae. In one ormore embodiments, one or more support arms may create or exert a tensionforce to native chordae. In one or more embodiments, the central portionand/or one or more of its components, such as one or more support arms,may be designed to engage and/or push against one or more native valvecommissures.

In one or more embodiments, valve prosthesis may comprise an inflow,inlet, upstream, or proximal portion connected, coupled, positioned,and/or located at a proximal end or proximal end portion of the centralportion of the valve prosthesis. In one or more embodiments, the inflowportion and/or one or more of its components may contact, engage,fixate, capture, clamp, pierce, hold, position, and/or seal the valveprosthesis to one or more heart structures and/or tissues such as atrialtissue, ventricle tissue, valve tissue, annulus tissue, the floor of anatrium, and/or the floor of a ventricle. For example, the inflow portionand/or one or more of its components may engage atrial tissue if thevalve prosthesis is positioned in a native mitral valve whereas theinflow portion and/or one or more of its components may engage ventricletissue if the valve prosthesis is positioned in a native aortic valve.In one or more embodiments, the inflow portion and/or one or more of itscomponents may exert one or more forces, for example, radial and/oraxial forces, to one or more heart structures and/or heart tissues. Inone or more embodiments, the inflow portion and/or one or more of itscomponents may comprise one or more fixation elements or members such asanchors, barbs, clips, prongs, grommets, sutures, and/or screws. In oneor more embodiments, the inflow portion and/or one or more of itscomponents may comprise one or more longitudinal or cross-sectionalshapes, such as a geometric shape, a non-geometric shape, a tubularshape, a cylindrical shape, a circular shape, an elliptical shape, anoval shape, a triangular shape, a rectangular shape, a hexagonal shape,a square shape, a polygonal shape, a funnel shape, a nozzle shape, aD-shape, an S-shape, a saddle shape, a simple geometric shape, and/or acomplex geometric shape. In one or more embodiments, the inflow portionand/or one or more of its components may be designed to deform to theshape of the native anatomy when the valve prosthesis is implanted. Forexample, the inflow portion may deform from a pre-delivery circularshape to a post-delivery D-shape following the delivery of the valveprosthesis to a native mitral valve. In one or more embodiments, theinflow portion and/or one or more of its components may comprise aframe, a framework, or stent-like structure, as described herein. In oneor more embodiments, the inflow portion and/or one or more of itscomponents may comprise, be covered with, be coated with, or be attachedor coupled to one or more materials, as described herein. In one or moreembodiments, the inflow portion and/or one or more of its components maycomprise one or more support arms, components, or members as describedherein. In one or more embodiments, one or more support arms maycomprise one or more cantilever components or portions. In one or moreembodiments, the inflow portion and/or one or more of its components,such as one or more support arms, may be designed to engage and/or pushagainst the native valve annulus. In one or more embodiments, the inflowportion and/or one or more of its components, such as one or moresupport arms, may be designed to engage, capture, clamp, hold, and/ortrap one or more native valve leaflets. In one or more embodiments, theinflow portion and/or one or more of its components, such as one or moresupport arms, may be designed to engage, capture, clamp, hold, and/ortrap one or more native chordae. In one or more embodiments, one or moresupport arms may create or exert a tension force to native chordae. Inone or more embodiments, the inflow portion and/or one or more of itscomponents, such as one or more support arms, may be designed to engageand/or push against one or more native valve commissures.

In one or more embodiments, valve prosthesis may comprise an outflow,outlet, downstream, or distal portion connected, coupled, positioned,and/or located at a distal end or distal end portion of the centralportion of the valve prosthesis. In one or more embodiments, the outflowportion and/or one or more of its components may contact, engage,fixate, capture, clamp, pierce, hold, position, and/or seal the valveprosthesis to one or more heart structures and/or tissues such as atrialtissue, ventricle tissue, valve tissue, valve leaflet tissue, annulustissue, and/or chordae tissue. For example, the outflow portion and/orone or more of its components may engage leaflet tissue, chordae tissue,and/or ventricle tissue if the valve prosthesis is positioned in anative mitral valve whereas the outflow portion and/or one or more ofits components may engage leaflet tissue and/or aortic tissue if thevalve prosthesis is positioned in a native aortic valve. In one or moreembodiments, the outflow portion and/or one or more of its componentsmay exert one or more forces, for example, radial and/or axial forces,to one or more heart structures and/or heart tissues. In one or moreembodiments, the outflow portion and/or one or more of its componentsmay comprise one or more fixation elements or members such as anchors,barbs, prongs, clips, grommets, sutures, and/or screws. In one or moreembodiments, the outflow portion and/or one or more of its componentsmay comprise one or more longitudinal or cross-sectional shapes, such asa geometric shape, a non-geometric shape, a tubular shape, a cylindricalshape, a circular shape, an elliptical shape, an oval shape, atriangular shape, a rectangular shape, a hexagonal shape, a squareshape, a polygonal shape, a funnel shape, a nozzle shape, a D-shape, anS-shape, a saddle shape, a simple geometric shape, and/or a complexgeometric shape. In one or more embodiments, the outflow portion and/orone or more of its components may be designed to deform to the shape ofthe native anatomy when the valve prosthesis is implanted. For example,the outflow portion may deform from a pre-delivery circular shape to apost-delivery D-shape following the delivery of the valve prosthesis toa native mitral valve. In one or more embodiments, the outflow portionand/or one or more of its components may comprise a frame, a framework,or stent-like structure, as described herein. In one or moreembodiments, the outflow portion and/or one or more of its componentsmay comprise, be covered with, be coated with, or be attached or coupledto one or more materials, as described herein. In one or moreembodiments, the outflow portion and/or one or more of its componentsmay comprise one or more support arms, components, or members asdescribed herein. In one or more embodiments, the outflow portion and/orone or more of its components, such as one or more support arms, may bedesigned to engage, capture, clamp, hold, and/or trap one or more nativevalve leaflets. In one or more embodiments, the outflow portion and/orone or more of its components, such as one or more support arms, may bedesigned to engage, capture, clamp, hold, and/or trap one or more nativechordae. In one or more embodiments, one or more support arms may createor exert a tension force to native chordae. In one or more embodiments,the outflow portion and/or one or more of its components, such as one ormore support arms, may be designed to engage and/or push against one ormore native valve commissures. In one or more embodiments, the outflowportion and/or one or more of its components, such as one or moresupport arms, may be designed to engage and/or push against the nativevalve annulus. In one or more embodiments, one or more support arms maycomprise one or more cantilever components or portions.

Valve prosthesis embodiments disclosed herein illustrate support armshaving a single arm, support arms with inner and outer support arms andvariations of structures thereof, and/or one more pairs of support armshaving various structures and attachment points for providing variousfunctions when implanted. It should be understood that the illustratedembodiments hereof are not limited to the number or configuration ofsupport arms illustrated in each figure and that one or more supportarms, one or more pairs of support arms and/or the various structurestherefore may be substituted across the various embodiments disclosedherein without departing from the scope hereof.

In one or more embodiments, valve prosthesis may comprise one or moresupport arms for engaging one or more native valve leaflets. In one ormore embodiments, valve prosthesis may comprise one or more support armsfor engaging one or more native chordae. In one or more embodiments,valve prosthesis may comprise one or more support arms for engaging oneor more native valve commissures. In one or more embodiments, valveprosthesis may comprise one or more support arms for engaging a nativevalve annulus. In one or more embodiments, valve prosthesis may compriseone or more support arms for engaging one or more native valve tissuesor structures. For example, one or more support arms may engage orinteract with valve leaflets, chordae, commissures and/or annulus. Inone or more embodiments, valve prosthesis may comprise one or moresupport arms for engaging one or more heart tissues or structures. Inone or more embodiments, valve prosthesis may comprise one or moresupport arms for engaging the pulmonary artery. In one or moreembodiments, valve prosthesis may comprise one or more support arms forengaging the aorta.

In one or more embodiments, one or more support arms may be coupled orconnected to the central portion, the inflow portion and/or the outflowportion of valve prosthesis. In one or more embodiments, valveprosthesis may comprise one or more support arms that may apply one ormore forces such as a radial force, an axial force, a lateral force, aninward force, an outward force, an upstream force, and/or a downstreamforce to one or more valve structures, valve tissues, heart structuresand/or heart tissues. In some embodiments, one or more support arms, asdescribed herein, may be considerably longer, shorter, wider, ornarrower than shown. In some embodiments, one or more support arms, asdescribed herein, may be narrower at the base, bottom or proximal endportion where the support arms couple to the inflow portion, centralportion and/or the outflow portion of the valve prosthesis and wider atthe top or distal end portion of the support arm. In some embodiments,one or more support arms, as described herein, may be wider at the base,bottom, or proximal end portion where the support arms couple to theinflow portion, central portion and/or the outflow portion of the valveprosthesis and narrower at the top or distal end portion of the supportarm. In some embodiments, one or more support arms, as described herein,may be configured to be a shape and size that can provide a positioningfunction, valve leaflet capturing function, a stabilization function, ananti-migration function, and/or an anchoring function for valveprosthesis in accordance herewith when the prosthesis is deployed at anative valve site. In some embodiments, one or more support arms, asdescribed herein, may interact, engage, capture, clamp, push against oneor more native tissues or structures such as valve leaflets, chordae,annulus, ventricle, and/or atrium. In some embodiments, one or moresupport arms, as described herein, may comprise a first portion thatextends in a forward direction and a second portion that extends in abackward direction. In some embodiments, one or more support arms, asdescribed herein, may comprise a first portion that extends in abackward direction and a second portion that extends in a forwarddirection. In some embodiments, one or more support arms, as describedherein, may comprise one or more portions that may extend horizontally,longitudinally, axially, circumferentially, inward, outward, forward,and/or backward. In some embodiments, one or more support arms, asdescribed herein, may comprise more than one configuration. For example,one or more embodiments of one or more support arms, as describedherein, may extend in first direction in a delivery configuration and ina second direction in a deployed configuration. In one example, a firstor delivery direction may be a forward direction and a second ordeployed direction may be a backward direction. In another example, afirst or delivery direction may be a backward direction and a second ordeployed direction may be a forward direction. In one or moreembodiments, one or more support arms, as described herein, may comprisea first shape in a delivery configuration and a second shape in adeployed configuration. For example, a first or delivery shape may be astraight shape and a second or deployed shape may be a curved shape.

In some embodiments, one or more support arms, as described herein, maycomprise one or more portions that comprise one or more spiral shapes,s-shapes, c-shapes, u-shapes, V-shapes, loop shapes, tine shapes, and/orprong shapes. In some embodiments, one or more support arms, asdescribed herein, may comprise a curved, rounded, and/or flared distalend portion. In some embodiments, one or more support arms, as describedherein, may be connected, coupled, attached, and/or extend from one ormore locations positioned on the inflow portion, the central portionand/or the outflow portion of the valve prosthesis. In some embodiments,one or more support arms, as described herein, may comprise at least aportion that may comprise at least one free end not attached or coupledto the frame of the valve prosthesis. In one or more embodiments, one ormore support arms and/or one or more of components of a support arm maycomprise one or more fixation elements or members such as anchors,barbs, prongs, clips, grommets, sutures, and/or screws. In one or moreembodiments, one or more support arms and/or one or more of componentsof a support arm may comprise, for example, one or more active and/orpassive fixation elements or members.

In one or more embodiments, a valve prosthesis and/or one or more of itscomponents such as one or more support arms may comprise a first acuteconfiguration and a second chronic configuration. For example, an acuteconfiguration may correspond to an initial and/or early implantconfiguration and a chronic configuration may correspond to alater-in-time configuration following the implant of the valveprosthesis. In some embodiments, one or more support arms, as describedherein, may be narrower at the base, bottom, or proximal end portion ina first acute configuration and then wider at the base, bottom, orproximal end portion in a second chronic configuration. FIG. 52 is aside view of a valve prosthesis 5200 in accordance with an embodimenthereof in a first or acute deployed configuration that after a certainperiod of time transforms into a second or chronic deployedconfiguration (not shown). Valve prosthesis 5200 has an inflow portion5202 and an outflow or central portion 5204, which holds a prostheticvalve component 5220 (depicted by dashed lines) for blocking flow in onedirection to regulate blood flow through valve prosthesis 5200. Valveprosthesis 5200 includes a self-expanding frame, framework or stent 5210that defines the inflow and outflow portions 5202, 5204 and includes apair of support arms 5206 (only one of which is shown) that extend froma distal end 5205 thereof. In the embodiment shown in FIG. 52, supportarms 5206 may include a first or outer U-shaped support arm 5286 and asecond or inner U-shaped support arm 5288 that may each bend or rotatemore than ninety degrees with respect to a compressed, deliveryconfiguration during deployment, as previously discussed above. Thenative valve leaflets may be held by support arms 5206, as describedabove, such that the chordae tendinae (CT) may be held in tension orunder load thereby. Any of the tent concepts described above may be usedwith the embodiment of FIG. 52 in order to prevent the chordae (CT) fromrubbing against frame 5210 and more particular from contacting supportarms 5206.

Valve prosthesis 5200 provides a means for counteracting stressrelaxation or loss of load and/or stretching that occurs over time inbiological tissue, and particularly such stretching and/or stressrelaxation that may occur in the chordae (CT) when the valve prosthesisis used to replace a mitral valve. Frame 5210 of valve prosthesis 5200may have two or more unique configurations to counteract stressrelaxation and/or stretching in which one configuration is acute orshort-term and occurs upon initial deployment or implantation while theother configuration is chronic or long-term and evolves or occurs overtime. Stated another way, frame 5210 may be described as a time-releasedframe having two distinct configurations, one acute configuration andone chronic configuration wherein the acute configuration may beconfigured to prevent paravalvular leakage (PVL) and damage to theanatomy in the short-term, while the chronic configuration may beconfigured to provide for optimal long-term performance to includepreventing paravalvular leakage (PVL) over a longer period. In anembodiment, the transition from the acute configuration to the chronicconfiguration may occur within the same time period as the stressrelaxation of the chordae.

In order to provide the first, acute or short-term deployedconfiguration upon initial deployment at a native valve site and for aperiod of time thereafter, valve prosthesis 5200 may include one or moreresorbable or biodegradable sutures 5293 attached at outflow end 5205 offrame 5210 to radially constrain or hold the outflow end of support arms5206 and/or frame 5210 to a reduced diameter or a narrower dimensionthan its fully expanded state. As previously described the support armstension the chordae upon implantation of valve prosthesis 5200; however,in the embodiment of FIG. 52 valve prosthesis 5200 in the acuteconfiguration temporarily constrains support arms 5206 from fullyexpanding with resorbable or biodegradable sutures 5293, which shortensthe papillary muscle-chordae-valve leaflet-chordae-papillary-musclelength to prevent damage to the anatomy upon initial deployment and fora short-term thereafter. In some embodiments valve prosthesis 5200 mayinclude first and second resorbable or biodegradable sutures 5293A,5293B that radially constrain inner and outer support arms 5288, 5286,respectively, at outflow end 5205 in order to constrain support arms5206 to a reduced diameter or dimension when the valve prosthesis is inthe acute deployed configuration. In some embodiments, first and secondresorbable or biodegradable sutures 5293A, 5293B may have differentdissolution rates in order to provide a more gradual transition to thechronic configuration, or stated another way to permit a more gradualexpansion of support arms 5206 and/or frame 5210. In some embodiments,one of the first and second sutures 5293A, 5293B may degrade in therange of 10 to 14 days to partially release the support arms and/orframe and the other or remaining of the first and second sutures 5293A,5293B may degrade in the range of 28 to 35 days to fully release thesupport arms and/or frame and thereby obtain the chronic configuration.It should be understood by the foregoing description that the chronicconfiguration of valve prosthesis 5200 evolves over time as one or moreof the resorbable or biodegradable sutures 5293 are absorbed ordegraded. The chronic configuration has a longer papillarymuscle-chordae-valve leaflet-chordae-papillary muscle length than theacute configuration due to the wider dimension of the unconstrained,fully expanded support arms 5206, which is intended to tension thechordae back to the initial optimal load to prevent chronic paravalvularleakage (PVL) without acutely damaging the sub-valvular anatomy. Inaccordance with embodiments hereof, any support arm and/or framedisclosed herein may have an acute configuration and a chronicconfiguration to include support arms of any of the inflow portions, andcentral or outflow portions described above.

In one or more embodiments, the valve prosthesis may comprise one ormore active and/or passive fixation elements or members such as anchors,barbs, prongs, clips, grommets, sutures, and/or screws. In one or moreembodiments, one or more active and/or passive fixation elements ormembers may be delivered separately from the valve prosthesis. In one ormore embodiments, one or more active and/or passive fixation elements ormembers may be delivered during the valve prosthesis implant procedure.In one or more embodiments, one or more active and/or passive fixationelements or members may be delivered after the valve prosthesis implantprocedure. In one or more embodiments, one or more active and/or passivefixation elements or members may be delivered using the valve prosthesisdelivery system. In one or more embodiments, one or more active fixationelements or members may be activated by pushing, pulling, twisting,screwing and/or turning motion or movement. In one or more embodiments,one or more fixation elements or members may be released or engaged viaan unsheathing, an unsleeving, a dissolving, and/or a degrading action.In one or more embodiments, one or more active and/or passive fixationelements or members may be delivered using a fixation element deliverysystem. In one or more embodiments, one or more active and/or passivefixation elements or members may be coupled, connected, and/or attachedto the valve prosthesis stent or frame. In one or more embodiments, thevalve prosthesis stent or frame may comprise a unitary structure thatcomprises one or more active and/or passive fixation elements. In one ormore embodiments, one or more active and/or passive fixation elementsmay be coupled, connected, and/or attached to the valve prosthesis skirtand/or graft material. In one or more embodiments, one or more fixationelements or members may be designed to increasingly engage one or moreheart tissues and/or structures via any movement of the valve prosthesisrelative to heart tissue and/or structures during one or more cardiaccycles. For example, a barbed fixation element that further embedsitself into tissue via movement of the valve prosthesis relative totissue in one direction and then resists movement of the valveprosthesis relative to tissue in the opposite direction.

The choice of materials for the various heart valve prostheses describedherein can be informed by the requirements of mechanical properties,temperature sensitivity, biocompatibility, moldability properties, orother factors apparent to a person having ordinary skill in the art. Forexample, one more of the parts (or a portion of one of the parts),components, and/or portions can be made from suitable plastics, such asa suitable thermoplastic, suitable metals, and/or other suitablematerials.

In order to transform between an initial compressed configuration andthe deployed configuration shown in the figures hereof, frames andsupport arms in accordance with embodiments described herein may beformed from a self-expanding material that has a mechanical memory toreturn to the deployed configuration. Accordingly in accordance withembodiments hereof, frames may be made from stainless steel, apseudo-elastic metal such as a nickel titanium alloy or nitinol, or aso-called super alloy, which may have a base metal of nickel, cobalt,chromium, or other metal. Mechanical memory may be imparted to thetubular structure that forms the frames by thermal treatment to achievea spring temper in stainless steel, for example, or to set a shapememory in a susceptible metal alloy, such as nitinol, or a polymer, suchas any of the polymers disclosed in U.S. Pat. Appl. Pub. No.2004/0111111 to Lin, which is incorporated by reference herein in itsentirety. In accordance with other embodiments hereof, a frame of avalve prosthesis can be formed entirely or in part by a biocompatiblematerial. In accordance with other embodiments hereof, one or moreportions of a frame of a valve prosthesis can be self-expandable and/orballoon expandable.

In accordance with embodiments hereof, the valve body or component andvalve leaflets thereof can be formed, for example, from one or morebiocompatible synthetic materials, synthetic polymers, autograft tissue,homograft tissue, xenograft tissue, or one or more other suitablematerials. In some embodiments, the valve body or component and valveleaflets thereof can be formed, for example, from bovine, porcine,equine, ovine, and/or other suitable animal tissues. In accordance withembodiments hereof, the valve body or component and valve leafletsthereof may be made of or formed from a natural material obtained from,for example, heart valves, aortic roots, aortic walls, aortic leaflets,pericardial tissue, such as pericardial patches, bypass grafts, bloodvessels, intestinal submucosal tissue, umbilical tissue and the likefrom humans or animals. In accordance with other embodiments hereof,synthetic materials suitable for use as valve components and valveleaflets thereof include DACRON® polyester commercially available fromInvista North America S.A.R.L. of Wilmington, Del., other clothmaterials, nylon blends, polymeric materials, and vacuum depositionnitinol fabricated materials. In an embodiment, valve body or componentand valve leaflets thereof can be made of an ultra-high molecular weightpolyethylene material commercially available under the trade designationDYNEEMA from Royal DSM of the Netherlands. With certain leafletmaterials, it may be desirable to coat one or both sides of the leafletwith a material that will prevent or minimize overgrowth. It is furtherdesirable that the leaflet material is durable and not subject tostretching, deforming, or fatigue. In accordance with other embodimentshereof, the valve body or component can comprise one or more valveleaflets. For example, the valve body or component can be in the form ofa tri-leaflet bovine pericardium valve, a bi-leaflet valve, or anothersuitable valve. In accordance with other embodiments hereof, the valvebody or component can comprise three leaflets that are fastened togetherat enlarged lateral end regions to form commissural joints, with theunattached edges forming coaptation edges of the valve body. Inaccordance with other embodiments hereof, the prosthetic valve leafletscan be fastened to a skirt of a graft material, which in turn can beattached to the frame.

In accordance with embodiments hereof, the graft material or portionsthereof may be a low-porosity woven fabric, such as polyester, DACRON®polyester, or polytetrafluoroethylene (PTFE), which creates a one-wayfluid passage when attached to the frame of the valve prosthesis. In anembodiment, the graft material or portions thereof may be a looser knitor woven fabric, such as a polyester or PTFE knit, which can be utilizedwhen it is desired to provide a medium for tissue ingrowth and theability for the fabric to stretch to conform to a curved surface. Inanother embodiment, polyester velour fabrics may alternatively be usedfor the graft material or portions thereof, such as when it is desiredto provide a medium for tissue ingrowth on one side and a smooth surfaceon the other side. These and other appropriate cardiovascular fabricsare commercially available from Bard Peripheral Vascular, Inc. of Tempe,Ariz., for example. In another embodiment, the graft material orportions thereof may be a natural material, such as pericardium oranother membranous tissue.

In accordance with embodiments hereof, valve-retaining tubular portionsand support arms of frames disclosed herein, as well as the graftmaterial and tent-like structures that may be associated therewith, maybe modified without departing from the scope of the present invention inview of the disclosures of one or more of U.S. application Ser. No.13/736,460 filed Jan. 8, 2013 to Igor Kovalsky et al., U.S. Appl. No.61/822,616 filed May 13, 2013 to Kshitija Garde et al., and U.S.application Ser. No. 13/572,842 filed Aug. 13, 2012 to Igor Kovalsky,each of which is incorporated by reference herein in its entirety.

In one or more embodiments, valve prosthesis and/or one or more of itscomponents or portions may comprise, be covered with, be coated with, orbe attached or coupled to one or more biocompatible materials orbiomaterials, for example, titanium, titanium alloys, Nitinol, TiNialloys, shape memory alloys, super elastic alloys, aluminum oxide,platinum, platinum alloys, stainless steels, stainless steel alloys,MP35N, elgiloy, haynes 25, stellite, pyrolytic carbon, silver carbon,glassy carbon, polymers or plastics such as polyamides, polycarbonates,polyethers, polyesters, polyolefins including polyethylenes orpolypropylenes, polystyrenes, polyurethanes, polyvinylchlorides,polyvinylpyrrolidones, silicone elastomers, fluoropolymers,polyacrylates, polyisoprenes, polytetrafluoroethylenes, polyethyleneterephthalates, fabrics such as woven fabrics, nonwoven fabrics, porousfabrics, semi-porous fabrics, nonporous fabrics, Dacron fabrics,polytetrafluoroethylene (PTFE) fabrics, polyethylene terephthalate (PET)fabrics, materials that promote tissue ingrowth, rubber, minerals,ceramics, hydroxapatite, epoxies, human or animal protein or tissue suchas collagen, laminin, elastin or fibrin, organic materials such ascellulose, or compressed carbon, and/or other materials such as glass,and the like. Materials that are not considered biocompatible may bemodified to become biocompatible by a number of methods well known inthe art. For example, coating a material with a biocompatible coatingmay enhance the biocompatibility of that material. Biocompatiblematerials or biomaterials are usually designed and constructed to beplaced in or onto tissue of a patient's body or to contact fluid of apatient's body. Ideally, a biocompatible material or biomaterial willnot induce undesirable reactions in the body such as blood clotting,tumor formation, allergic reaction, foreign body reaction (rejection) orinflammatory reaction; will have the physical properties such asstrength, elasticity, permeability, and flexibility required to functionfor the intended purpose; may be purified, fabricated and sterilizedeasily; will substantially maintain its physical properties and functionduring the time that it remains in contact with tissues or fluids of thebody.

In one or more embodiments, one or more surfaces of the valve prosthesisand/or one or more of its components or portions may comprise, becovered with, be coated with, or be attached or coupled to one or moreradioactive materials and/or biological agents, for example, ananticoagulant agent, an antithrombotic agent, a clotting agent, aplatelet agent, an anti-inflammatory agent, an antibody, an antigen, animmunoglobulin, a defense agent, an enzyme, a hormone, a growth factor,a neurotransmitter, a cytokine, a blood agent, a regulatory agent, atransport agent, a fibrous agent, a protein, a peptide, a proteoglycan,a toxin, an antibiotic agent, an antibacterial agent, an antimicrobialagent, a bacterial agent or component, hyaluronic acid, apolysaccharide, a carbohydrate, a fatty acid, a catalyst, a drug, avitamin, a DNA segment, a RNA segment, a nucleic acid, a lectin, anantiviral agent, a viral agent or component, a genetic agent, a ligandand/or a dye (which acts as a biological ligand). Biological agents maybe found in nature (naturally occurring) or may be chemicallysynthesized by a variety of methods well known in the art.

In one or more embodiments, valve prosthesis and/or one or more of itscomponents or portions may comprise, be coated with, be covered with, orbe attached or coupled to one or more biological cells or tissues, forexample, tissue cells, cardiac cells, contractile cells, muscle cells,heart muscle cells, smooth muscle cells, skeletal muscle cells,autologous cells, allogenic cells, xenogenic cells, stem cells,genetically engineered cells, non-engineered cells, mixtures of cells,precursor cells, immunologically neutral cells, differentiated cells,undifferentiated cells, natural tissue, synthetic tissue, animal tissue,human tissue, porcine tissue, equine tissue, porcine tissue, bovinetissue, ovine tissue, autologous tissue, allogenic tissue, xenogenictissue, autograft tissue, genetically engineered tissue, non-engineeredtissue, mixtures of tissues, cardiac tissue, pericardial tissue, cardiacvalve tissue, membranous tissue, and/or intestinal submucosa tissue. Inone or more embodiments, valve prosthesis and/or one or more of itscomponents or portions may comprise, be covered with, be coated with, orbe attached or coupled to one or more materials that promote the growthof cells and/or tissue. In one or more embodiments, the cell and/ortissue promoting materials may comprise, possess or be configured topossess physical characteristics such as size, shape, porosity, matrixstructure, fiber structure, and/or chemical characteristics such asgrowth factors, biological agents, that promote and/or aid, for example,in the adherence, proliferation and/or growth of desired cells and/ortissues in vivo following implantation or ex vivo prior to implantation.In one or more embodiments, the cell and/or tissue promoting materialsmay accelerate the healing response of the patient following theimplantation of the valve prosthesis. In one or more embodiments, thecell and/or tissue promoting materials may comprise pockets, parachutes,voids, and/or openings, for example, that may trap cells and/or tissuesand/or promote cells and/or tissues to proliferate, grow and/or heal.

In one or more embodiments, valve prosthesis and/or one or more of itscomponents or portions may comprise, be coated with, be covered with, beconstrained by, or be attached or coupled to a shape memory material, abioresorbable material, and/or a biodegradable material, such as anatural or synthetic biodegradable polymer, non-limiting examples ofwhich include polysaccharides such as alginate, dextran, cellulose,collagen, and chemical derivatives thereof, proteins such as albumin,and copolymer blends thereof, alone or in combination with syntheticpolymers, polyhydroxy acids, such as polylactides, polyglycolides andcopolymers thereof, poly(ethylene terephthalate), poly(hydroxybutyricacid); poly(hydroxyvaleric acid), poly[lactide-co-(E-caprolactone)];poly[glycolide-co-(E-caprolactone)], polycarbonates, poly(pseudo aminoacids); poly(amino acids); poly(hydroxyalkanoate)s, polyanhydrides;polyortho esters, and blends and copolymers thereof. In one or moreembodiments, one or more surfaces of the valve prosthesis and/or one ormore of its components or portions may comprise, be covered with, becoated with, or be attached or coupled to one or more glues and/oradhesives, such as a bioglue or bioadhesive used to help anchor and/orseal the valve prosthesis to native tissue.

In one or more embodiments, valve prosthesis and/or one or more of itscomponents or portions may be compressible and/or expandable, forexample, self-expandable, balloon expandable, or mechanicallyexpandable.

One or more of the valve prostheses described herein can be implantedinto an annulus of a native cardiac valve through a suitable deliverymethod. For example, the valve prosthesis can be implanted throughconventional open-heart surgery techniques. In some embodiments, thevalve prosthesis can be delivered percutaneously. For example, in somepercutaneous techniques, valve prosthesis can be compacted and loadedonto a delivery device for advancement through a patient's vasculature.The valve prosthesis can be delivered through an artery or vein, afemoral artery, a femoral vein, a jugular vein, a subclavian artery, anaxillary artery, an aorta, an atrium, and/or a ventricle. The valveprosthesis may be delivered via a transfemoral, transapical,transseptal, transatrial, transventrical, or transaortic procedure.

In some embodiments, the valve prosthesis can be deliveredtransfemorally. In such a delivery, the delivery device and the valveprosthesis can be advanced in a retrograde manner through the femoralartery and into the patient's descending aorta. A catheter can then beadvanced under fluoroscopic guidance over the aortic arch, through theascending aorta, into the left ventricle, and mid-way across thedefective mitral valve. Once positioning of the catheter is confirmed,the delivery device can deploy the valve prosthesis within the annulus.The valve prosthesis can then expand against and align the prosthesiswithin the annulus. In some embodiments, as the valve prosthesis isexpanded, it can trap leaflets against the annulus, which can retain thenative valve in a permanently open state.

In some embodiments, the valve prosthesis can be delivered via atransapical procedure. In a transapical procedure, a trocar or over-tubecan be inserted into a patient's left ventricle through an incisioncreated in the apex of the patient's heart. A dilator can be used to aidin the insertion of the trocar. In this approach, the native valve (forexample, the mitral valve) can be approached from the downstreamrelative to the blood flow. The trocar can be retracted sufficiently torelease the self-expanding valve prosthesis. The dilator can bepresented between the leaflets. The trocar can be rotated and adjustedto align the valve prosthesis in a desired alignment. The dilator can beadvanced into the left atrium to begin disengaging the proximal sectionof the valve prosthesis from the dilator.

In some embodiments, the valve prosthesis can be delivered via atransatrial procedure. In such a procedure, a dilator and trocar can beinserted through an incision made in the wall of the left atrium of theheart. The dilator and trocar can then be advanced through the nativevalve and into the left ventricle of heart. The dilator can then bewithdrawn from the trocar. A guide wire can be advanced through thetrocar to the point where the valve prosthesis comes to the end of thetrocar. The valve prosthesis can be advanced sufficiently to release theself-expanding frame from the trocar. The trocar can be rotated andadjusted to align the valve prosthesis in a desired alignment. Thetrocar can be withdrawn completely from the heart such that the valveprosthesis self-expands into position and can assume the function of thenative valve.

Mitral valve prosthesis in accordance with embodiments hereof may bedelivered via a transapical implantation procedure or via a transatrialimplantation procedure. Suitable transapical and/or transatrialimplantation procedures that may be adapted for use with mitral valveprosthesis described herein are disclosed in U.S. application Ser. No.13/572,842 filed Aug. 13, 2012 to Igor Kovalsky, U.S. Appl. Pub. No.2011/0208297 to Tuval et al., and U.S. Appl. Pub. No. 2012/0035722 toTuval et al, each of which is incorporated by reference herein in itsentirety.

In one or more embodiments of the present invention, valve prosthesisand/or one or more of its components or portions may be delivered, forexample, through a thoracotomy, a sternotomy, percutaneously,transvenously, arthroscopically, endoscopically, for example, through apercutaneous port, a stab wound or puncture, through a small incision,for example, in the chest, groin, abdomen, neck, leg, arm, or incombinations thereof. In one or more embodiments of the presentinvention, valve prosthesis and/or one or more of its components orportions may be delivered, for example, via a transvascular method, atransarterial method, a transvenous method, a transcardiac method, atransatrial method, a transventrical method, transapical method, atransseptal method, a transaortic method, a transcatheter method, asurgical method, a beating heart method, a stopped heart method, apump-assisted method, and/or a cardiopulmonary bypass method.

In one or more embodiments of the present invention, valve prosthesisand/or one or more of its components or portions may be positioned in,positioned through, and/or positioned adjacent to, for example, anatural valve, a native valve, a synthetic valve, a replacement valve, atissue valve, a mechanical valve, a mitral valve, an aortic valve, apulmonary valve, a tricuspid valve, a valve component, a valve annulus,a valve leaflet, chordae, and/or a valve commissure.

While various embodiments have been described above, it should beunderstood that they have been presented only as illustrations andexamples of the present invention, and not by way of limitation. It willbe apparent to persons skilled in the relevant art that various changesin form and detail can be made therein without departing from the spiritand scope of the invention. Thus, the breadth and scope of the presentinvention should not be limited by any of the above-described exemplaryembodiments, but should be defined only in accordance with the appendedclaims and their equivalents. It will also be understood that eachfeature of each embodiment discussed herein, and of each reference citedherein, can be used in combination with the features of any otherembodiment. All patents and publications discussed herein areincorporated by reference herein in their entirety.

1-25. (canceled)
 26. A valve prosthesis for implantation into a nativevalve site, the valve prosthesis comprising: a frame including anhourglass-shaped central portion with a reduced waist region, the frameincluding a plurality of struts and a plurality of crowns, with aplurality of openings formed by the plurality of struts and theplurality of crowns; and a skirt attached to the frame, the skirtextending over at least a portion of each opening of the plurality ofopenings, wherein endmost crowns of the plurality of crowns extendbeyond an endmost edge of the skirt.
 27. The valve prosthesis of claim26, wherein the frame further includes a first leaflet support arm beingconfigured to engage a first native valve leaflet and a second leafletsupport arm being configured to engage a second native valve leaflet,the second leaflet support arm being diametrically opposed to the firstleaflet support arm.
 28. The valve prosthesis of claim 27, wherein thefirst and second leaflet support arms each has an acute configurationwhen initially implanted in situ and a chronic configuration after beingimplanted in situ for a predetermined amount of time, wherein thechronic configuration differs from the acute configuration.
 29. Thevalve prosthesis of claim 26, wherein the skirt is a portion of a valvebody that is supported within the frame.
 30. The valve prosthesis ofclaim 29, wherein the valve body includes at least two valve leaflets.31. The valve prosthesis of claim 26, wherein the skirt is formed from alow-porosity woven fabric.
 32. The valve prosthesis of claim 26, whereinthe skirt is formed from pericardium.
 33. The valve prosthesis of claim26, wherein the frame includes an inflow end and an outflow end, andwherein the endmost crowns of the plurality of crowns form the outflowend of the valve prosthesis.
 34. The valve prosthesis of claim 26,wherein the frame includes an inflow end and an outflow end, and whereinfirst openings of the plurality of openings are disposed at the inflowend and second openings of the plurality of openings are disposed at theoutflow end, and wherein the first openings are larger than the secondopenings.
 35. The valve prosthesis of claim 26, wherein the centralregion is configured to pinch a muscular ridge of a native annulus whenimplanted therein.
 36. A valve prosthesis for implantation into a nativevalve site, the valve prosthesis comprising: a frame having an hourglassshape with a reduced waist region, the frame including a central portionsupporting the valve body, the central portion configured to fit withinan annulus of the native valve site, an inflow portion configured toengage an upstream side of the annulus and restrict movement of thevalve prosthesis in a downstream direction of blood flow at the nativevalve site, a first ventricular arm that outwardly extends from thereduced waist region of the frame, and a second ventricular arm thatoutwardly extends from the reduced waist region of the frame, the secondventricular arm being diametrically opposed to the first ventriculararm, each of the first and second ventricular arms being positionedalong a circumference of the central portion, wherein the hourglassshape of the frame is formed by the inflow portion and the first andsecond ventricular arms such that the frame pinches the annulus fromboth the atrial and ventricular sides of the annulus; and a valve bodysupported within the frame.
 37. The valve prosthesis of claim 36,wherein the frame further includes a first leaflet support arm beingconfigured to engage a first native valve leaflet and a second leafletsupport arm being configured to engage a second native valve leaflet,the second leaflet support arm being diametrically opposed to the firstleaflet support arm, wherein each of the first and second ventriculararms is positioned along a circumference of the central portion betweenthe first and second leaflet support arms.
 38. The valve prosthesis ofclaim 36, wherein the inflow portion of the frame and the first andsecond ventricular arms originate from a same node location of thecentral portion.
 39. The valve prosthesis of claim 36, wherein theinflow portion of the frame and the first and second ventricular armsoriginate from different node locations of the central portion such thata gap is present between the inflow portion of the frame and the firstand second ventricular arms within the reduced waist region.
 40. A valveprosthesis for implantation into a native valve site, the valveprosthesis comprising: a valve body; and a frame comprising, a centralportion supporting the valve body, the central portion configured to fitwithin an annulus of the native valve site, an inflow portion configuredto engage an upstream side of the annulus and restrict movement of thevalve prosthesis in a downstream direction of blood flow at the nativevalve site, a first leaflet support arm being configured to engage anative valve leaflet and restrict movement of the valve prosthesis in anupstream direction of blood flow at the native valve site, a secondleaflet support arm being configured to engage a native valve leafletand restrict movement of the valve prosthesis in an upstream directionof blood flow at the native valve site, the second leaflet support armbeing diametrically opposed to the first leaflet support arm, a firstcommissural engagement support arm extending from a distal end of theframe to provide ventricular fixation of the valve prosthesis within thenative valve site, and a second commissural engagement support armextending from the distal end of the frame to provide ventricularfixation of the valve prosthesis within the native valve site, the firstand second commissural engagement support arms being disposedside-by-side and positioned along a circumference of the central portionbetween the first and second leaflet support arms.
 41. The valveprosthesis of claim 40, wherein each of the first and second commissuralengagement support arms has a U-shape.
 42. The valve prosthesis of claim40, wherein the first and second commissural engagement support arms areconfigured to be deployed sequentially after deployment of the first andsecond leaflet support arms.